FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2477684080> ?p ?o ?g. }

• W2477684080 abstract "One third of non-small-cell lung cancer (NSCLC) patients develop bone metastasis and die within a year. Tumor growth in the bone microenvironment results in excessive bone resorption−osteolytic bone lesions, which releases many cytokines and growth factors stored in the bone matrix, such as transforming growth factor-β (TGF-β), which further stimulates metastatic tumor growth in the bone. It is not known how TGF-β signaling in resident cells of the bone microenvironment effect NSCLC-induced bone lesions. We found that blocking TGF-β signaling in cells of the myeloid lineage, LysMCre/Tgfbr2 knockout (KO), but not in cells of the mesenchymal lineage, Col1αcre/Tgfbr2 KO, decreases osteolytic bone lesion development of H1993 or H1975 NSCLC cells in a tibial-injected mouse model. In determining the mechanism by which LysMCre/Tgfbr2 KO decreases NSCLC bone lesion development, we demonstrated that basic-fibroblast growth factor (bFGF) of the mouse origin was significantly decreased in NSCLC injected tibiae of LysMCre/Tgfbr2 KO mice relative to controls. Exogenous bFGF partially rescues the reduced NSCLC bone lesions in these LysMCre/Tgfbr2 KO mice. bFGF is expressed by cells of the mesenchymal lineage, such as osteoblasts. However, bFGF has no effect on H1993 NSCLC cell proliferation. These data suggest that the decreases in NSCLC-induced bone lesions by loss of TGF-β signaling in myeloid lineage cells are dependent on the effects of bFGF on osteoblasts and osteoclasts. We therefore hypothesize that the regulation of bFGF expression in osteoblasts is indirect through a secreted myeloid-specific TGF-β signaling downstream target, collagen triple-helix repeat-containing 1 (Cthrc1). Cthrc1 is a TGF-β target gene and clastokine, which are proteins secreted by osteoclasts that couple osteoblasts. Cthrc1 is also a known biomarker for NSCLC progression and promotes NSCLC cell proliferation and invasion. We found Cthrc1 was significantly decreased in H1993-injected tibiae of LysMCre/Tgfbr2 KO mice relative to controls, and stimulates H1993 proliferation in a dose-dependent manner in vitro. Additionally, Cthrc1 is known to stimulate bone formation. However, the effect of Cthrc1 on osteoblasts is not known in the context of NSCLC bone metastasis. From our in vitro studies, we found that Cthrc1 has no significant effect on osteoblast differentiation, but significantly increases bFGF gene expression in MC3T3 cells. bFGF inhibits osteoblast differentiation, but stimulates osteoclast differentiation. We therefore conclude that myeloid-specific TGF-β signaling stimulates osteoclast Cthrc1 secretion, which promotes NSCLC tumor cell proliferation. Meanwhile, Cthrc1 increases bFGF expression from osteoblasts to inhibit osteoblast, but stimulate osteoclast differentiation. Taken together, these data suggests Cthrc1 is a potential novel target for effectively inhibiting NSCLC bone metastasis. Citation Format: Paul G. Daft, Xiangqi Meng, Alexandra Vander Ark, Austin Meadows, Xiaohong Li. Cthrc1 mediated by myeloid-specific TGF-β signaling stimulates NSCLC bone metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1565." @default.
• W2477684080 created "2016-08-23" @default.
• W2477684080 creator A5009246718 @default.
• W2477684080 creator A5019394181 @default.
• W2477684080 creator A5083729859 @default.
• W2477684080 creator A5084513075 @default.
• W2477684080 creator A5089318076 @default.
• W2477684080 date "2016-07-15" @default.
• W2477684080 modified "2023-09-25" @default.
• W2477684080 title "Abstract 1565: Cthrc1 mediated by myeloid-specific TGF-β signaling stimulates NSCLC bone metastasis" @default.
• W2477684080 doi "https://doi.org/10.1158/1538-7445.am2016-1565" @default.
• W2477684080 hasPublicationYear "2016" @default.
• W2477684080 type Work @default.
• W2477684080 sameAs 2477684080 @default.
• W2477684080 citedByCount "0" @default.
• W2477684080 crossrefType "proceedings-article" @default.
• W2477684080 hasAuthorship W2477684080A5009246718 @default.
• W2477684080 hasAuthorship W2477684080A5019394181 @default.
• W2477684080 hasAuthorship W2477684080A5083729859 @default.
• W2477684080 hasAuthorship W2477684080A5084513075 @default.
• W2477684080 hasAuthorship W2477684080A5089318076 @default.
• W2477684080 hasConcept C118131993 @default.
• W2477684080 hasConcept C121608353 @default.
• W2477684080 hasConcept C126322002 @default.
• W2477684080 hasConcept C170493617 @default.
• W2477684080 hasConcept C185592680 @default.
• W2477684080 hasConcept C198826908 @default.
• W2477684080 hasConcept C2775960820 @default.
• W2477684080 hasConcept C2776107976 @default.
• W2477684080 hasConcept C2777587049 @default.
• W2477684080 hasConcept C2777783956 @default.
• W2477684080 hasConcept C2779013556 @default.
• W2477684080 hasConcept C2779282312 @default.
• W2477684080 hasConcept C3020616263 @default.
• W2477684080 hasConcept C502942594 @default.
• W2477684080 hasConcept C71924100 @default.
• W2477684080 hasConcept C86803240 @default.
• W2477684080 hasConcept C95444343 @default.
• W2477684080 hasConceptScore W2477684080C118131993 @default.
• W2477684080 hasConceptScore W2477684080C121608353 @default.
• W2477684080 hasConceptScore W2477684080C126322002 @default.
• W2477684080 hasConceptScore W2477684080C170493617 @default.
• W2477684080 hasConceptScore W2477684080C185592680 @default.
• W2477684080 hasConceptScore W2477684080C198826908 @default.
• W2477684080 hasConceptScore W2477684080C2775960820 @default.
• W2477684080 hasConceptScore W2477684080C2776107976 @default.
• W2477684080 hasConceptScore W2477684080C2777587049 @default.
• W2477684080 hasConceptScore W2477684080C2777783956 @default.
• W2477684080 hasConceptScore W2477684080C2779013556 @default.
• W2477684080 hasConceptScore W2477684080C2779282312 @default.
• W2477684080 hasConceptScore W2477684080C3020616263 @default.
• W2477684080 hasConceptScore W2477684080C502942594 @default.
• W2477684080 hasConceptScore W2477684080C71924100 @default.
• W2477684080 hasConceptScore W2477684080C86803240 @default.
• W2477684080 hasConceptScore W2477684080C95444343 @default.
• W2477684080 hasLocation W24776840801 @default.
• W2477684080 hasOpenAccess W2477684080 @default.
• W2477684080 hasPrimaryLocation W24776840801 @default.
• W2477684080 hasRelatedWork W1661230647 @default.
• W2477684080 hasRelatedWork W1971393163 @default.
• W2477684080 hasRelatedWork W1989530383 @default.
• W2477684080 hasRelatedWork W2032774636 @default.
• W2477684080 hasRelatedWork W2039249160 @default.
• W2477684080 hasRelatedWork W2067746501 @default.
• W2477684080 hasRelatedWork W2067973073 @default.
• W2477684080 hasRelatedWork W2119219693 @default.
• W2477684080 hasRelatedWork W2127619759 @default.
• W2477684080 hasRelatedWork W2197188550 @default.
• W2477684080 hasRelatedWork W231025824 @default.
• W2477684080 hasRelatedWork W2335657655 @default.
• W2477684080 hasRelatedWork W2588790607 @default.
• W2477684080 hasRelatedWork W2729964056 @default.
• W2477684080 hasRelatedWork W2742532112 @default.
• W2477684080 hasRelatedWork W2764069724 @default.
• W2477684080 hasRelatedWork W2807886233 @default.
• W2477684080 hasRelatedWork W2813743998 @default.
• W2477684080 hasRelatedWork W2980760005 @default.
• W2477684080 hasRelatedWork W3014721604 @default.
• W2477684080 isParatext "false" @default.
• W2477684080 isRetracted "false" @default.
• W2477684080 magId "2477684080" @default.
• W2477684080 workType "article" @default.