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• W2758886073 abstract "The vasohibin ( VASH ) family consists of two genes, VASH 1 and VASH 2 . VASH 1 is mainly expressed in vascular endothelial cells and suppresses angiogenesis in an autocrine manner, whereas VASH 2 is mainly expressed in cancer cells and exhibits pro‐angiogenic activity. Employing adenomatous polyposis coli gene mutant mice, we recently reported on the role of Vash2 in the spontaneous formation of intestinal tumors. In this study, we used K19‐Wnt1/C2mE ( Gan ) mice and examined the role of Vash2 in spontaneous gastric cancer formation. Gan mice spontaneously develop gastric tumors by activation of Wnt and prostaglandin E2 signaling pathways in gastric mucosa after 30 weeks of age. Expression of Vash2 mRNA was significantly increased in gastric tumor tissues compared with normal stomach tissues. When Gan mice were crossed with the Vash2 ‐deficient ( Vash2 LacZ/LacZ ) strain, gastric cancer formation was significantly suppressed in Vash2 LacZ/LacZ Gan mice. Normal composition of gastric mucosa was partially maintained in Vash2 LacZ/LacZ Gan mice. Knockout of Vash2 caused minimal reduction of tumor angiogenesis but a significant decrease in cancer‐associated fibroblasts ( CAF ) in tumor stroma. DNA microarray analysis and real‐time RT ‐ PCR showed that mRNA levels of epiregulin (Ereg) and interleukin‐11 (Il11) were significantly downregulated in gastric tumors of Vash2 L acZ/LacZ Gan mice. Furthermore, conditioned medium of gastric cancer cells stimulated migration of and α‐smooth muscle actin expression in fibroblasts, whereas conditioned medium of VASH 2 knockdown cells attenuated these effects in vitro . These results suggest that VASH 2 plays an important role in gastric tumor progression via the accumulation of CAF accompanying upregulation of EREG and IL ‐11 expression." @default.
• W2758886073 created "2017-10-06" @default.
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• W2758886073 date "2017-10-21" @default.
• W2758886073 modified "2023-10-17" @default.
• W2758886073 title "Requisite role of vasohibin‐2 in spontaneous gastric cancer formation and accumulation of cancer‐associated fibroblasts" @default.
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• W2758886073 doi "https://doi.org/10.1111/cas.13411" @default.
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