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• W4319308510 abstract "Many proliferative, invasive, and immune tolerance mechanisms that support normal human pregnancy are also exploited by malignancies to establish a nutrient supply and evade or edit the host immune response. In addition to the shared capacity for invading through normal tissues, both cancer cells and cells of the developing placenta create a microenvironment supportive of both immunologic privilege and angiogenesis. Systemic alterations in immunity are also detectable, particularly with respect to a helper T cell type 2 polarization evident in advanced cancers and midtrimester pregnancy. This review summarizes the similarities between growth and immune privilege in cancer and pregnancy and identifies areas for further investigation. Our PubMed search strategy included combinations of terms such as immune tolerance, pregnancy, cancer, cytokines, angiogenesis, and invasion. We did not place any restrictions on publication dates. The knowledge gained from analyzing similarities and differences between the physiologic state of pregnancy and the pathologic state of cancer could lead to identification of new potential targets for cancer therapeutic agents. Many proliferative, invasive, and immune tolerance mechanisms that support normal human pregnancy are also exploited by malignancies to establish a nutrient supply and evade or edit the host immune response. In addition to the shared capacity for invading through normal tissues, both cancer cells and cells of the developing placenta create a microenvironment supportive of both immunologic privilege and angiogenesis. Systemic alterations in immunity are also detectable, particularly with respect to a helper T cell type 2 polarization evident in advanced cancers and midtrimester pregnancy. This review summarizes the similarities between growth and immune privilege in cancer and pregnancy and identifies areas for further investigation. Our PubMed search strategy included combinations of terms such as immune tolerance, pregnancy, cancer, cytokines, angiogenesis, and invasion. We did not place any restrictions on publication dates. The knowledge gained from analyzing similarities and differences between the physiologic state of pregnancy and the pathologic state of cancer could lead to identification of new potential targets for cancer therapeutic agents. A substantial body of literature exists describing the mechanisms cancer cells use to escape apoptosis and migrate through normal structures while evading a host immune response. What is not well known, however, is how these complex and interrelated mechanisms are orchestrated, starting with modulation of the immune response within the tumor microenvironment and ending with migration and proliferation of cancer cells at distant sites. One potential model to further study how a single malignant cell could proliferate and then metastasize undetected within a host is that of normal human pregnancy, in which the developing placenta invades the uterus and a semiallogeneic fetus escapes rejection from the maternal immune system.1Medawar PB Some immunological and endocrinological problems raised by the evolution of viviparty in vertebrates.Symp Soc Exp Biol. 1953; 7: 320-338Google Scholar A multitude of immunomodulatory properties of the fetomaternal interface (placenta) have evolved to allow the survival of the immunologically distinct fetus to parturition without an attack from the maternal immune system. The similarities between the mechanisms involved in fetomaternal and tumor-associated immunologic tolerance are intriguing and suggest a common pattern; however, neither system of immune evasion is perfect. A clear example of placental failure to protect the fetus against maternal immunity is that of Rh incompatibility. In multiparous women sensitized against fetal Rh antigens, re-exposure to fetal Rh antigens with subsequent pregnancy may lead to hemolytic disease of the newborn and fetal death.2Clarke CA Immunology of pregnancy: significance of blood group incompatibility between mother and foetus.Proc R Soc Med. 1968; 61: 1213-1216PubMed Google Scholar Such imperfections of shared mechanisms of immune tolerance between pregnancy and cancer suggest that cancer rejection via immunologic means may be possible, even considering the myriad mechanisms extending immunologic privilege to the fetus as well as cancer cells. This review summarizes the parallels in proliferation, invasion, and immune privilege between cancer and pregnancy by first detailing shared characteristics of fetal-derived trophoblast cells of the placenta and tumor cells. It then describes the similarities between tolerogenic systems within the tumor microenvironment and the fetomaternal interface. Finally, it provides an overview of the evidence for systemic immune modulation in cancer and pregnancy and suggests the implications of these similarities in designing an integrated approach to cancer therapy. Our PubMed search strategy included combinations of terms such as immune tolerance, pregnancy, cancer, cytokines, angiogenesis, and invasion. We also searched for articles on cellular subsets, including natural killer (NK) cells, dendritic cells (DCs), regulatory T cells (Treg), and other lymphocyte populations with respect to their presence and function in pregnancy and cancer. We did not place any restrictions on publication dates. A better understanding of how the maternal immune system is altered during the normal processes of implantation, gestation, and labor may translate into individualized, novel therapies aimed at restoring immune competency in patients with advanced malignancies. Five days after fertilization, the human zygote forms into a structure consisting of 2 primary cell lines: the inner cellmass (or embryoblast) and the trophoblast.3Staun-Ram E Shalev E Human trophoblast function during the implantation process.Reprod Biol Endocrinol. 2005 Oct; 3: 56Crossref PubMed Scopus (74) Google Scholar Trophoblast cells constitute the outer layer of the blastocyst, rapidly proliferating and invading the maternal endometrial decidua around day 7. A monolayer of cytotrophoblast cells surrounds the embryonic disc as the embryo completely embeds beneath the uterine decidua. By day 9, cytotrophoblast cells have differentiated into 2 distinct cell types: the syncytiotrophoblast and the extravillous trophoblast (EVT). The multinucleated syncytiotrophoblast cells form the external layer and are terminally differentiated. These cells are involved in fetomaternal nutrient exchanges and endocrine functions (such as β-human chorionic gonadotropic production). In contrast, EVT cells have a proliferative and invasive phenotype, migrating through the syncytiotrophoblast into the uterine wall to anchor the placenta beginning around day 14 after implantation.4Lunghi L Ferretti ME Medici S Biondi C Vesce F Control of human trophoblast function.Reprod Biol Endocrinol. 2007 Feb 8; 5: 6Crossref PubMed Scopus (72) Google Scholar These EVT cells display a phenotype strikingly similar to cancer cells with their capacity for proliferation, migration, and establishment of a blood supply, making them a compelling model for oncologic comparison (Figure). This review highlights several shared characteristics of trophoblast and tumor cells and discusses them in the context of existing or developmental targeted cancer therapeutics (Table 1).TABLE 1Tumorlike Attributes of the Human Trophoblast Cells and a Selection of Representative Targeted Cancer Therapeutic Strategies in Use or DevelopmentaHLA = human leukocyte antigen. For expansion of all gene symbols, see Glossary of Genetics Terminology at the end of the article.Shared trophoblast-tumor attributeMechanismTargeted therapeutic strategyDrug/compound namebData regarding drug compounds are from Mayo Clin Proc,53 unless a citation is given to indicate otherwise.Self-sufficiency in growth signalsActivation of MAPK pathwayInhibition of RAS-RAF-MEK-ERK signalingSorafenib; ARRY-142886; PLX-4032; XL281; RAF265; PD03259015Fecher LA Amaravadi RK Flaherty KT The MAPK pathway in melanoma.Curr Opin Oncol. 2008; 20: 183-189Crossref PubMed Scopus (79) Google ScholarActivation of PI3K-AKT pathwayInhibition of RAS-PI3K-AKT-MTOR signalingQuercitin, XL147, and XL765; GDC-0941; BEZ235; PX-8666Ihle NT Powis G Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy.Mol Cancer Ther. 2009; 8: 1-9Crossref PubMed Scopus (82) Google Scholar; sirolimus; everolimus; temsirolimusFAK activationFAK inhibitionTAE2267Liu TJ LaFortune T Honda T et al.Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo.Mol Cancer Ther. 2007; 6: 1357-1367Crossref PubMed Scopus (92) Google Scholar; dasatinibHGF autocrine loopHGF or C-MET inhibitionOA-5D58Martens T Schmidt NO Eckerich C et al.A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo.Clin Cancer Res. 2006; 12: 6144-6152Crossref PubMed Scopus (134) Google Scholar; AMG-1029Jun HT Sun J Rex K et al.AMG 102, a fully human anti-hepatocyte growth factor/scatter factor neutralizing antibody, enhances the efficacy of temozolomide or docetaxel in U-87 MG cells and xenografts.Clin Cancer Res. 2007; 13: 6735-6742Crossref PubMed Scopus (68) Google Scholar; SGX-523; PF-0234106; XL880EGF autocrine loopEGF or EGFR inhibitionErlotinib; cetuximab; panitumumab; XL647IGF autocrine loopIGF or IGFR inhibitionAEW54110García-Echeverría C Pearson MA Marti A et al.In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase.Cancer Cell. 2004; 5: 231-239Abstract Full Text Full Text PDF PubMed Scopus (328) Google ScholarCSF autocrine loopCSF1 or CSF1R inhibitionGW258011Conway JG McDonald B Parham J et al.Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580.Proc Natl Acad Sci U S A. 2005 Nov 1; 102 (Epub 2005 Oct 25.): 16078-16083Crossref PubMed Scopus (69) Google Scholar; CYC1026812Irvine KM Burns CJ Wilks AF Su S Hume DA Sweet MJ A CSF-1 receptor kinase inhibitor targets effector functions and inhibits pro-inflammatory cytokine production from murine macrophage populations.FASEB J. 2006 Sep; 20 (Epub 2006 Jul 28.): 1921-1923Crossref PubMed Scopus (24) Google ScholarPDGF autocrine loopPDGF or PDGFR inhibitionAZD2171; pazopanib; sorafenib; sunitinib: E7080; ZD6474; AG-013736VEGF autocrine loopVEGF or VEGFR inhibitionBevacizumab; RAF265; BMS-690514Insensitivity to antigrowth signalsTGF-β pathway activationTGF-β2 blockadeAP 1200913Schlingensiepen KH Fischer-Blass B Schmaus S Ludwig S Antisense therapeutics for tumor treatment: the TGF-beta2 inhibitor AP 12009 in clinical development against malignant tumors.Recent Results Cancer Res. 2008; 177: 137-150Crossref PubMed Google Scholar; LY-215729914Yingling JM Blanchard KL Sawyer JS Development of TGF-β signalling inhibitors for cancer therapy.Nat Rev Drug Discov. 2004; 3: 1011-1022Crossref PubMed Scopus (272) Google ScholarCDKCDK inhibitionSNS-03215Chen R Wierda WG Chubb S et al.Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia.Blood. 2009 May 7; 113 (Epub 2009 Feb 20.): 4637-4645Crossref PubMed Scopus (42) Google Scholar; AT751916Squires MS Feltell RE Wallis NG et al.Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.Mol Cancer Ther. 2009 Feb; 8 (Epub 2009 Jan 27.): 324-332Crossref PubMed Scopus (32) Google Scholar;flavopiridolSMADALK inhibition leading to decreased SMAD phosphorylationA 83-0117Tojo M Hamashima Y Hanyu A et al.The ALK-5 inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-β.Cancer Sci. 2005; 96: 791-800Crossref PubMed Scopus (91) Google ScholarEvasion of apoptosisIGF1R signalingIGF1R blockadeConcept reviewed by Werhova and Haluska18Weroha SJ Haluska P IGF-1 receptor inhibitors in clinical trials–early lessons.J Mammary Gland Biol Neoplasia. 2008 Dec; 13 (Epub 2008 Nov 21.): 471-483Crossref PubMed Scopus (82) Google Scholar; R1507: CP-751,87119Haluska P Shaw HM Batzel GN et al.Phase I dose escalation study of the anti insulin-like growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors.Clin Cancer Res. 2007; 13: 5834-5840Crossref PubMed Scopus (154) Google Scholar20Lacy MQ Alsina M Fonseca R et al.Phase I, pharmacokinetic and pharmacodynamic study of the anti-insulinlike growth factor type 1 Receptor monoclonal antibody CP-751,871 in patients with multiple myeloma.J Clin Oncol. 2008 Jul; 26 (Epub 2008 May 12A.): 3196-3203Crossref PubMed Scopus (92) Google ScholarPDGFR signalingPDGFR blockadeImatinib; sorafenib; sunitinib; E7080; ZD6474; AG-013736; pazopanibBCL2BCL2 inhibitionOblimersenSurvivinSurvivin inhibitionYM-155; terameprocolXIAPXIAP antisenseAEG35156EndoreduplicationMaintain p53 integrity; Aurora kinase inhibition; induction of p21 (waf1/cip1)Nutlin-3a (promotes endoreduplication)21Shen H Moran DM Maki CG Transient nutlin-3a treatment promotes endoreduplication and the generation of therapy-resistant tetraploid cells.Cancer Res. 2008; 68: 8260-8268Crossref PubMed Scopus (18) Google Scholar; VX-68022Gizatullin F Yao Y Kung V Harding MW Loda M Shapiro GI The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function.Cancer Res. 2006; 66: 7668-7677Crossref PubMed Scopus (106) Google Scholar; theaflavins23Prasad S Kaur J Roy P Kalra N Shukla Y Theaflavins induce G2/M arrest by modulating expression of p21waf1/cip1, cdc25C and cyclin B in human prostate carcinoma PC-3 cells.Life Sci. 2007 Oct 13; 81 (Epub 2007 Sep 15.): 1323-1331Crossref PubMed Scopus (22) Google ScholarLimitless replicative potentialTelomeraseTelomerase inhibitionGRN163L; RHPS4HGF–C-MET signalingMET inhibitionPF-0234106Sustained angiogenesisVEGFR signalingVEGF inhibitionBevacizumab; sorafenib; sunitinib; E7080; ZD6474; AG-013736; pazopanib; IMC-1121B; AZD2171; CHIR-265; ABT-510; BMS-690514; XL880; afliberceptHIF-1αHIF-1α inhibitionPX-478PGFPGF inhibitionTB-40324Phase I study on monoclonal antibody TB-403 directed against PlGF in patients with solid tumours. ClinicalTrials.gov Web site. http://clinicaltrials.gov/ct2/show/NCT00702494. First received June 19, 2008. Last updated September 5, 2008. Accessed June 17, 2009.Google ScholarFGFFGF inhibitionPI-88Tissue invasionIntegrinsα2 integrin inhibition; αν integrin inhibition; ανβ3 + ανβ5 integrin inhibition; ανβ3 integrin inhibitionE 7820; CNTO 95; cilengitide; abergrin (MEDI 522)MMPsDown-regulation of MMPsCurcumin25Yodkeeree S Chaiwangyen W Garbisa S Limtrakul P Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA.J Nutr Biochem. 2009 Feb; 20 (Epub 2008 May 20.): 87-95Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar; Saponins26Lee KJ Hwang SJ Choi JH Jeong HG Saponins derived from the roots of Platycodon grandiflorum inhibit HT-1080 cell invasion and MMPs activities: regulation of NF-κB activation via ROS signal pathway.Cancer Lett. 2008 Sep; 268 (Epub May 21.): 233-243Abstract Full Text Full Text PDF PubMed Scopus (27) Google ScholarWnt signalingCyclooxygenase-2 inhibitionCelecoxib27Tuynman JB Vermeulen L Boon EM et al.Cyclooxygenase-2 inhibition inhibits c-Met kinase activity and Wnt activity in colon cancer.Cancer Res. 2008; 68: 1213-1220Crossref PubMed Scopus (59) Google ScholarHSP273-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitionLipophilic statin medications: atorvastatin, simvastatin, lovastatin, or fluvastatin28Karp I Behlouli H Lelorier J Pilote L Statins and cancer risk.Am J Med. 2008; 121: 302-309Abstract Full Text Full Text PDF PubMed Scopus (76) Google ScholarImmune evasionDecreased HLA class I expressionIncreased HLA class I expressionGamma irradiation29Chiriva-Internati M Grizzi F Pinkston J et al.Gamma-radiation upregulates MHC class I/II and ICAM-I molecules in multiple myeloma cell lines and primary tumors.In Vitro Cell Dev Biol Anim. 2006; 42: 89-95Crossref PubMed Scopus (8) Google Scholar; samarium-153-ethylenedi-aminetetramethylenephosphonate30Chakraborty M Wansley EK Carrasquillo JA et al.The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing.Clin Cancer Res. 2008; 14: 4241-4249Crossref PubMed Scopus (17) Google Scholar; DNA-demethylating agent 5-aza-2'-deoxycytidine31Adair SJ Hogan KT Treatment of ovarian cancer cell lines with 5-aza-2′-deoxycytidine upregulates the expression of cancer-testis antigens and class I major histocompatibility complex-encoded molecules.Cancer Immunol Immunother. 2009 Apr; 58 (Epub 2008 Sep 13.): 589-601Crossref PubMed Scopus (26) Google ScholarNonclassical HLAG expressionNeutralization of soluble HLAG or reduced gene transcription of HLAGNone yet developed, but 5-aza-2'-deoxycytidine increases HLAG in leukemia cell lines with unknown clinical immunomodulatory impact32Poláková K Bandzuchová E Kuba D Russ G Demethylating agent 5-aza-2′-deoxycytidine activates HLA-G expression in human leukemia cell lines.Leuk Res. 2009 Apr; 33 (Epub 2008 Sep 26.): 518-524Abstract Full Text Full Text PDF PubMed Scopus (11) Google ScholarPGE2Decreased PGE2 synthesisCelecoxib33Zweifel BS Davis TW Ornberg RL Masferrer JL Direct evidence for a role of cyclooxygenase 2-derived prostaglandin E2 in human head and neck xenograft tumors.Cancer Res. 2002; 62: 6706-6711PubMed Google ScholarComplement regulatory proteinsNeutralization of miniantibodies to CD55 and CD59MB55 and MB59 tested in mouse models only at time of writing of this manuscript34Macor P Tripodo C Zorzet S et al.In vivo targeting of human neutralizing antibodies against CD55 and CD59 to lymphoma cells increases the antitumor activity of rituximab.Cancer Res. 2007; 67: 10556-10563Crossref PubMed Scopus (51) Google ScholarIDODecreased IDO expression, IDO blockadeCelecoxib,35Basu GD Tinder TL Bradley JM et al.Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO.J Immunol. 2006; 177: 2391-2402PubMed Google Scholar1-methyl D-tryptophan36Jia L Schweikart K Tomaszewski J et al.Toxicology and pharmacokinetics of 1-methyl-d-tryptophan: absence of toxicity due to saturating absorption.Food Chem Toxicol. 2008 Jan; 46 (Epub 2007 Aug 10.): 203-211Crossref PubMed Scopus (24) Google ScholarCD44 expression (also soluble)CD44 ligationAnti-CD44 monoclonal antibodies37Charrad RS Li Y Delpech B et al.Ligation of the CD44 adhesion molecule reverses blockage of differentiation in human acute myeloid leukemia.Nat Med. 1999; 5: 669-676Crossref PubMed Scopus (99) Google ScholarMUC1MUC1 radioimmunotherapyRadioimmunotherapy with MUC1 monoclonal antibody38Song EY Qu CF Rizvi SM et al.Bismuth-213 radioimmunotherapy with C595 anti-MUC1 monoclonal antibody in an ovarian cancer ascites model.Cancer Biol Ther. 2008 Jan; 7 (Epub 2007 Oct 8.): 76-80Crossref PubMed Google Scholar39Richman CM Denardo SJ O'Donnell RT et al.High-dose radioimmunotherapy combined with fixed, low-dose paclitaxel in metastatic prostate and breast cancer by using a MUC-1 monoclonal antibody, m170, linked to indium-111/yttrium-90 via a cathepsin cleavable linker with cyclosporine to prevent human anti-mouse antibody.Clin Cancer Res. 2005; 11: 5920-5927Crossref PubMed Scopus (36) Google ScholarNeuropilin 1 and 2Neuropilin receptor blockadeNone yet available, but concept reviewed by Mac Gabhann and Popel40Mac Gabhann F Popel AS Targeting neuropilin-1 to inhibit VEGF signaling in cancer: comparison of therapeutic approaches.PLOS Comput Biol. 2006 Dec 29; 2 (Epub 2006 Nov 16.): e180Crossref PubMed Scopus (25) Google ScholarB7H1B7H1 blockadeNone yet available, but concept reviewed by Thompson et al41Thompson RH Dong H Kwon ED Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy.Clin Cancer Res. 2007 Jan; 13: 709s-715sCrossref PubMed Scopus (34) Google ScholarFASLRecombinant FASLAPO01042Verbrugge I Wissink EH Rooswinkel RW et al.Combining radiotherapy with APO010 in cancer treatment.Clin Cancer Res. 2009 Mar 15; 15 (Epub 2009 Mar 10.): 2031-2038Crossref PubMed Scopus (19) Google ScholarCCL5CCL5 vaccine adjuvantEngineered CCL5 superagonist43Dorgham K Abadie V Iga M Hartley O Gorochov G Combadière B Engineered CCR5 superagonist chemokine as adjuvant in anti-tumor DNA vaccination.Vaccine. 2008 Jun 19; 26 (Epub 2008 Apr 24.): 3252-3260Crossref PubMed Scopus (5) Google ScholarTRAILRTRAILR2 agonistLexatumumabTIM3TIM3 blockadeNone yet available, but concept reviewed by Anderson44Anderson DE TIM-3 as a therapeutic target in human inflammatory diseases.Expert Opin Ther Targets. 2007; 11: 1005-1009Crossref PubMed Scopus (15) Google ScholarTLRSynthetic TLR agonistsAmpligen (TLR3 agonist)45Navabi H Jasani B Reece A et al.A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro.Vaccine. 2009 Jan 1; 27 (Epub 2008 Oct 31.): 107-115Crossref PubMed Scopus (34) Google Scholar; imiquimod (TLR7 agonist)46Prins RM Craft N Bruhn KW et al.The TLR-7 agonist, imiquimod, enhances dendritic cell survival and promotes tumor antigen-specific T cell priming: relation to central nervous system antitumor immunity.J Immunol. 2006; 176: 157-164PubMed Google ScholarGalectinsGalectin inhibitionGCS-100 (Galectin 3 antagonist)47Chauhan D Li G Podar K et al.A novel carbohydrate-based therapeutic GCS-100 overcomes bortezomib resistance and enhances dexamethasone-induced apoptosis in multiple myeloma cells.Cancer Res. 2005; 65: 8350-8358Crossref PubMed Scopus (45) Google Scholar; thiodigalactoside ester derivatives48Delaine T Cumpstey I Ingrassia L et al.Galectin-inhibitory thiodigalactoside ester derivatives have antimigratory effects in cultured lung and prostate cancer cells.J Med Chem. 2008; 51: 8109-8114Crossref PubMed Scopus (23) Google ScholarCD200CD200 antibodyALXN600049Kretz-Rommel A Qin F Dakappagari N Cofiell R Faas SJ Bowdish KS Blockade of CD200 in the presence or absence of antibody effector function: implications for anti-CD200 therapy.J Immunol. 2008; 180: 699-705PubMed Google ScholarSDF1 (also known as CXCL12)CXCR4 (CXCL12 receptor) antagonismPlerixafor50De Clercq E Potential clinical applications of the CXCR4 antagonist bicyclam AMD3100.Mini Rev Med Chem. 2005; 5: 805-824Crossref PubMed Scopus (59) Google Scholar; CTCE-990851Richert MM Vaidya KS Mills CN et al.Inhibition of CXCR4 by CTCE-9908 inhibits breast cancer metastasis to lung and bone.Oncol Rep. 2009; 21: 761-767PubMed Google ScholarOsteopontinDown-regulation of osteopontin expressionSmall interfering RNA therapy52Gong M Lu Z Fang G Bi J Xue X A small interfering RNA targeting osteopontin as gastric cancer therapeutics.Cancer Lett. 2008 Dec 8; 272 (Epub 2008 Aug 9.): 148-159Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholara HLA = human leukocyte antigen. For expansion of all gene symbols, see Glossary of Genetics Terminology at the end of the article.b Data regarding drug compounds are from Mayo Clin Proc,53Sekulic A Haluska Jr, P Miller AJ Melanoma Study Group of Mayo Clinic Cancer Center et al.Malignant melanoma in the 21st century: the emerging molecular landscape.Mayo Clin Proc. 2008; 83: 825-846Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar unless a citation is given to indicate otherwise. Open table in a new tab Like tumor cells, trophoblast cells have a very high proliferative capacity and exhibit molecular characteristics found in rapidly dividing cancer cells.54Bulmer JN Morrison L Johnson PM Expression of the proliferation markers Ki67 and transferrin receptor by human trophoblast populations.J Reprod Immunol. 1988; 14: 291-302Abstract Full Text PDF PubMed Scopus (47) Google Scholar For example, increased telomerase activity, typically not observed to a substantial degree in normal somatic cells, is detectable in 85% of human cancers.55Kim NW Piatyszek MA Prowse KR et al.Specific association of human telomerase activity with immortal cells and cancer.Science. 1994; 266: 2011-2015Crossref PubMed Google Scholar In fact, the intracellular concentration of telomerase is exponentially related to the proliferative capacity of a cell.56Blagoev KB Cell proliferation in the presence of telomerase.PLoS One. 2009; 4 (Epub 2009 Feb 27.): e4622Crossref PubMed Google Scholar In human pregnancy, telomerase activity is highest during the first trimester and decreases with maturation of the placenta.57Kyo S Takakura M Tanaka M et al.Expression of telomerase activity in human chorion.Biochem Biophys Res Commun. 1997; 241: 498-503Crossref PubMed Scopus (38) Google Scholar Survivin, a protein that promotes proliferation and inhibits apoptosis, is overexpressed in many cancers58Li F Ambrosini G Chu EY et al.Control of apoptosis and mitotic spindle checkpoint by survivin.Nature. 1998; 396: 580-584Crossref PubMed Scopus (1264) Google Scholar and is also up-regulated by trophoblast cells.59Lehner R Bobak J Kim NW Shroyer AL Shroyer KR Localization of telomerase hTERT protein and survivin in placenta: relation to placental development and hydatidiform mole.Obstet Gynecol. 2001; 97: 965-970Crossref PubMed Scopus (25) Google Scholar Inhibition of survivin by knockdown with small interfering RNA leads to a marked decrease in proliferation introphoblast cell lines.60Fest S Brachwitz N Schumacher A et al.Supporting the hypothesis of pregnancy as a tumor: survivin is upregulated in normal pregnant mice and participates in human trophoblast proliferation.Am J Reprod Immunol. 2008; 59: 75-83Crossref PubMed Scopus (13) Google Scholar A similar decrease in proliferation is seen with survivin in small interfering RNA treatment of prostate,61Shen J Liu J Long Y et al.Knockdown of survivin expression by siRNAs enhances chemosensitivity of prostate cancer cells and attenuates its tumorigenicity.Acta Biochim Biophys Sin (Shanghai). 2009; 41: 223-230Crossref PubMed Scopus (17) Google Scholar glioma,62Zhen HN Li LW Zhang W et al.Short hairpin RNA targeting survivin inhibits growth and angiogenesis of glioma U251 cells.Int J Oncol. 2007; 31: 1111-1117PubMed Google Scholar non-Hodgkin lymphoma,63Congmin G Mu Z Yihui M Hanliang L Survivin–an attractive target for RNAi in non-Hodgkin's lymphoma, Daudi cell line as a model.Leuk Lymphoma. 2006; 47: 1941-1948Crossref PubMed Scopus (8) Google Scholar cervical cancer cells, and breast cancer cells.64Li QX Zhao J Liu JY et al.Survivin stable knockdown by siRNA inhibits tumor cell growth and angiogenesis in breast and cervical cancers.Cancer Biol Ther. 2006 Jul; 5 (Epub 2006 Jul 9.): 860-866Crossref PubMed Google Scholar Both survivin and telomerase levels are dramatically higher in hydatidiform moles than in normal placentas, providing insight into the potential involvement of these 2 different mechanisms in neoplastic transformation.59Lehner R Bobak J Kim NW Shroyer AL Shroyer KR Localization of telomerase hTERT protein and survivin in placenta: relation to placental development and hydatidiform mole.Obstet Gynecol. 2001; 97: 965-970Crossref PubMed Scopus (25) Google Scholar Another pathway supportive of both trophoblast and cancer cell proliferation is the IGF pathway (for expansion of all gene symbols, see Glossary of Genetics Terminology at the end of the article). By binding to the IGF1R on cytotrophoblast cells, IGF stimulates proliferation through the MAPK pathway and survival via activation of the PI3K pathway.65Forbes K Westwood M Baker PN Aplin JD Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta.Am J Physiol Cell Physiol. 2008 Jun; 294 (Epub 2008 Apr 9.): C1313-C1322Crossref PubMed Scopus (48) Google Scholar Normally, levels of IGF are tightly regulated by IGF-binding proteins and protease pregnancy-associated plasma protein A, a binding protein.66Boldt HB Conover CA Pregnancy-associated plasma protein-A (PAPP-A): a local regulator of IGF bioavailability through cleavage of IGFBPs.Growth Horm IGF Res. 2007 Feb; 17 (Epub 2007 Jan 10.): 10-18Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Loss of binding protein regulation may contribute to the malignant phenotype.67Pollak M Insulin and insulin-like growth factor signalling in neoplasia.Nat Rev Cancer. 2008; 8: 915-928Crossref PubMed Scopus (603) Google Scholar In cancer cells, the IGF1R pathway is not only mitogenic and antiapoptotic but is involved in protecting cancer cells from damaging effects of chemotherapy and radiation, potentially as a result of its effects on downstream signaling pathways.68Tao Y Pinzi V Bourhis J Deutsch E Mechanisms of disease: signaling of the insulin-like growth factor 1 receptor pathway–therapeutic perspectives in cancer.Nat Clin Pract Oncol. 2007; 4: 591-602Crossref PubMed Scopus (97) Google Scholar Additionally, the fetal form of the insulin receptor IR-A, which is highly expressed in fetal tissues and responsive to IGF2, is also a member of the IGF-signaling system.69Hill DJ Petrik J Arany E Growth factors and the regulation of fetal growth.Diabetes Care. 1998; 21: B60-B69PubMed Google Scholar In many cancers, including those of the breast and ovary, dysregulation of this fetal form of the insulin receptor becomes the predominant isoform leading to IGF2-stimulated proliferation and survival.70Papa V Pezzino V Costantino A et al.Elevated insulin receptor content in human breast cancer.J Clin Invest. 1990; 86: 1503-1510Crossref PubMed Google Scholar, 71Kalli KR Conover C" @default.
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• W4319308510 title "Cancer and Pregnancy: Parallels in Growth, Invasion, and Immune Modulation and Implications for Cancer Therapeutic Agents" @default.
• W4319308510 cites W1500273736 @default.
• W4319308510 cites W1510063171 @default.
• W4319308510 cites W1535191542 @default.
• W4319308510 cites W1541333106 @default.
• W4319308510 cites W1544282464 @default.
• W4319308510 cites W1547504566 @default.
• W4319308510 cites W1551826730 @default.
• W4319308510 cites W1568276869 @default.
• W4319308510 cites W1575826191 @default.
• W4319308510 cites W1582505011 @default.
• W4319308510 cites W1587249246 @default.
• W4319308510 cites W1620585649 @default.
• W4319308510 cites W1662899239 @default.
• W4319308510 cites W1669486342 @default.
• W4319308510 cites W1762620449 @default.
• W4319308510 cites W1882089686 @default.
• W4319308510 cites W1893364625 @default.
• W4319308510 cites W1907872725 @default.
• W4319308510 cites W1956923614 @default.
• W4319308510 cites W1964930836 @default.
• W4319308510 cites W1968444058 @default.
• W4319308510 cites W1968550069 @default.
• W4319308510 cites W1970241639 @default.
• W4319308510 cites W1970264868 @default.
• W4319308510 cites W1970410047 @default.
• W4319308510 cites W1970455281 @default.
• W4319308510 cites W1970674279 @default.
• W4319308510 cites W1973951521 @default.
• W4319308510 cites W1975306842 @default.
• W4319308510 cites W1976675985 @default.
• W4319308510 cites W1977283269 @default.
• W4319308510 cites W1982361212 @default.
• W4319308510 cites W1983195932 @default.
• W4319308510 cites W1983273171 @default.
• W4319308510 cites W1984532045 @default.
• W4319308510 cites W1985078311 @default.
• W4319308510 cites W1985683054 @default.
• W4319308510 cites W1986259737 @default.
• W4319308510 cites W1986414754 @default.
• W4319308510 cites W1988173241 @default.
• W4319308510 cites W1991761823 @default.
• W4319308510 cites W1993199678 @default.
• W4319308510 cites W1995431719 @default.
• W4319308510 cites W1996063613 @default.
• W4319308510 cites W1996810856 @default.
• W4319308510 cites W1998086182 @default.
• W4319308510 cites W1999030960 @default.
• W4319308510 cites W1999090873 @default.
• W4319308510 cites W2000971601 @default.
• W4319308510 cites W2003778314 @default.
• W4319308510 cites W2004032916 @default.
• W4319308510 cites W2004837178 @default.
• W4319308510 cites W2005230990 @default.
• W4319308510 cites W2005425489 @default.
• W4319308510 cites W2005603155 @default.
• W4319308510 cites W2006184289 @default.
• W4319308510 cites W2006909912 @default.
• W4319308510 cites W2007196716 @default.
• W4319308510 cites W2007964976 @default.
• W4319308510 cites W2008705941 @default.
• W4319308510 cites W2009057486 @default.
• W4319308510 cites W2009328663 @default.
• W4319308510 cites W2010074376 @default.
• W4319308510 cites W2011722454 @default.
• W4319308510 cites W2011996641 @default.
• W4319308510 cites W2012041649 @default.
• W4319308510 cites W2015632272 @default.
• W4319308510 cites W2015959969 @default.
• W4319308510 cites W2016064855 @default.
• W4319308510 cites W2018151362 @default.
• W4319308510 cites W2018155127 @default.
• W4319308510 cites W2018234318 @default.
• W4319308510 cites W2020366122 @default.
• W4319308510 cites W2020634893 @default.
• W4319308510 cites W2021582501 @default.
• W4319308510 cites W2022238295 @default.
• W4319308510 cites W2023164440 @default.
• W4319308510 cites W2023548671 @default.
• W4319308510 cites W2024849496 @default.
• W4319308510 cites W2026095495 @default.
• W4319308510 cites W2026273485 @default.
• W4319308510 cites W2027813788 @default.
• W4319308510 cites W2028695120 @default.
• W4319308510 cites W2031923120 @default.
• W4319308510 cites W2032233271 @default.
• W4319308510 cites W2032655351 @default.
• W4319308510 cites W2035248621 @default.
• W4319308510 cites W2035401673 @default.
• W4319308510 cites W2035427613 @default.

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