Matches in SemOpenAlex for { <https://semopenalex.org/work/W4317387908> ?p ?o ?g. }
- W4317387908 abstract "Profound resistance to chemotherapy remains a major challenge in achieving better clinical outcomes for patients with pancreatic ductal adenocarcinoma (PDAC). Recent studies indicate that gemcitabine (GEM) resistance is promoted both by pancreatic stellate cells (PSCs) and through increased glycolysis. However, it remains unknown whether PSCs affect GEM sensitivity via glycolytic regulation.Human pancreatic cancer cell (PCC) lines (BxPC-3, Capan-2, HPAF-II, Mia PaCa-2, Panc-1, SW-1990) were exposed to three different PSC-conditioned media (PSC-CM; PSC-1, PSC-2, HPaSteC), following either pre-treatment with glycolysis inhibitor NV-5440 or transfection for transient silencing of key glycolytic regulators (LDHA and MCT4). Proliferation, glucose transport, extracellular lactate, and GEM sensitivity were assessed. Protein expression was determined by Western blot and immunostaining. Moreover, secreted proteins in PSC-CMs were profiled by mass spectrometry (MS).While exposure to PSC-CMs did not affect glucose transport in PCCs, it increased their lactate release and proliferation, and reduced the sensitivity for GEM. Both NV-5440 treatment and transient silencing of LDHA and MCT4 inhibited these PSC-induced changes in PCCs. MS analysis identified 688 unique proteins with differential expression, of which only 87 were common to the three PSC-CMs. Most PSC-secreted proteins were extracellular matrix-related, including SPARC, fibronectin, and collagens. Moreover, exposure to PSC-CMs increased the phosphorylation of ERK in PCCs, but the treatment of PCCs with the MEK/ERK inhibitor PD98059 resulted in a reduction of PSC-CM-induced glycolysis and improved GEM sensitivity.The study findings suggest that PSC-secreted factors promote both glycolysis and GEM resistance in PCCs, and that glycolysis inhibition by NV-5440 and blocking of ERK phosphorylation by PD98059 protect PCCs from PSC-CM-induced loss of GEM sensitivity. Taken together, PSCs appear to promote GEM resistance in PDAC via glycolysis. Thus, targeting glycolysis may improve the effect of chemotherapy in PDAC." @default.
- W4317387908 created "2023-01-19" @default.
- W4317387908 creator A5005839019 @default.
- W4317387908 creator A5011620635 @default.
- W4317387908 creator A5013277239 @default.
- W4317387908 creator A5016991473 @default.
- W4317387908 creator A5033697679 @default.
- W4317387908 creator A5052962931 @default.
- W4317387908 creator A5053683423 @default.
- W4317387908 creator A5068127094 @default.
- W4317387908 date "2023-01-19" @default.
- W4317387908 modified "2023-09-30" @default.
- W4317387908 title "Pancreatic stellate cell-induced gemcitabine resistance in pancreatic cancer is associated with LDHA- and MCT4-mediated enhanced glycolysis" @default.
- W4317387908 cites W1829491214 @default.
- W4317387908 cites W1959380048 @default.
- W4317387908 cites W1967218392 @default.
- W4317387908 cites W1969836970 @default.
- W4317387908 cites W2027550738 @default.
- W4317387908 cites W2038009564 @default.
- W4317387908 cites W2040789365 @default.
- W4317387908 cites W2047621859 @default.
- W4317387908 cites W2059049492 @default.
- W4317387908 cites W2077950977 @default.
- W4317387908 cites W2081923494 @default.
- W4317387908 cites W2099598957 @default.
- W4317387908 cites W2115240134 @default.
- W4317387908 cites W2127675410 @default.
- W4317387908 cites W2144635981 @default.
- W4317387908 cites W2147924229 @default.
- W4317387908 cites W2164385704 @default.
- W4317387908 cites W2168992025 @default.
- W4317387908 cites W2223535266 @default.
- W4317387908 cites W2316252168 @default.
- W4317387908 cites W2408928001 @default.
- W4317387908 cites W2512815522 @default.
- W4317387908 cites W2561583042 @default.
- W4317387908 cites W2568414132 @default.
- W4317387908 cites W2579131879 @default.
- W4317387908 cites W2594036641 @default.
- W4317387908 cites W2608485495 @default.
- W4317387908 cites W2619018292 @default.
- W4317387908 cites W2735063286 @default.
- W4317387908 cites W2765808518 @default.
- W4317387908 cites W2769094265 @default.
- W4317387908 cites W2786455179 @default.
- W4317387908 cites W2895983744 @default.
- W4317387908 cites W2902532424 @default.
- W4317387908 cites W2908458492 @default.
- W4317387908 cites W2949931852 @default.
- W4317387908 cites W2951582017 @default.
- W4317387908 cites W2968207922 @default.
- W4317387908 cites W2970631186 @default.
- W4317387908 cites W2971848759 @default.
- W4317387908 cites W2972439987 @default.
- W4317387908 cites W2976596173 @default.
- W4317387908 cites W2978476976 @default.
- W4317387908 cites W2984799663 @default.
- W4317387908 cites W2985216317 @default.
- W4317387908 cites W3008650849 @default.
- W4317387908 cites W3042568371 @default.
- W4317387908 cites W3047578130 @default.
- W4317387908 cites W3089206890 @default.
- W4317387908 cites W3107671643 @default.
- W4317387908 cites W3108081045 @default.
- W4317387908 cites W3128972922 @default.
- W4317387908 cites W4200180827 @default.
- W4317387908 cites W4207072204 @default.
- W4317387908 cites W4211253487 @default.
- W4317387908 doi "https://doi.org/10.1186/s12935-023-02852-7" @default.
- W4317387908 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36658582" @default.
- W4317387908 hasPublicationYear "2023" @default.
- W4317387908 type Work @default.
- W4317387908 citedByCount "5" @default.
- W4317387908 countsByYear W43173879082023 @default.
- W4317387908 crossrefType "journal-article" @default.
- W4317387908 hasAuthorship W4317387908A5005839019 @default.
- W4317387908 hasAuthorship W4317387908A5011620635 @default.
- W4317387908 hasAuthorship W4317387908A5013277239 @default.
- W4317387908 hasAuthorship W4317387908A5016991473 @default.
- W4317387908 hasAuthorship W4317387908A5033697679 @default.
- W4317387908 hasAuthorship W4317387908A5052962931 @default.
- W4317387908 hasAuthorship W4317387908A5053683423 @default.
- W4317387908 hasAuthorship W4317387908A5068127094 @default.
- W4317387908 hasBestOaLocation W43173879081 @default.
- W4317387908 hasConcept C104317684 @default.
- W4317387908 hasConcept C119056186 @default.
- W4317387908 hasConcept C11960822 @default.
- W4317387908 hasConcept C121608353 @default.
- W4317387908 hasConcept C126322002 @default.
- W4317387908 hasConcept C185592680 @default.
- W4317387908 hasConcept C20251656 @default.
- W4317387908 hasConcept C2780210213 @default.
- W4317387908 hasConcept C2780258809 @default.
- W4317387908 hasConcept C502942594 @default.
- W4317387908 hasConcept C55493867 @default.
- W4317387908 hasConcept C57074206 @default.
- W4317387908 hasConcept C62112901 @default.
- W4317387908 hasConcept C62231903 @default.
- W4317387908 hasConcept C71924100 @default.
- W4317387908 hasConcept C86803240 @default.