THBS4/integrin α2 axis mediates BM-MSCs to promote angiogenesis in gastric cancer associated with chronic Helicobacter pylori infection.
THBS4/integrin α2 axis mediates BM-MSCs to promote angiogenesis in gastric cancer associated with chronic Helicobacter pylori infection.
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DOI：
10.18632/aging.203334
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发表时间：
2021-08-14
期刊：
影响因子：
--
通讯作者：
Lin R
中科院分区：
文献类型：
--
作者：
He L;Wang W;Shi H;Jiang C;Yao H;Zhang Y;Qian W;Lin R
Background: BM-MSCs contribute to Helicobacter pylori (H. pylori)-induced gastric cancer, but their mechanism is still unclear. The aim of our study was to investigate the specific role and mechanism of BM-MSCs in H. pylori-induced gastric cancer. Main methods: Mice received total bone marrow transplants and were then infected with H. pylori. BM-MSCs were extracted and transplanted into the gastric serosal layer of mice chronically infected with H. pylori. Hematoxylin and eosin staining, immunohistochemistry staining and immunofluorescence were performed to detect tumor growth and angiogenesis in mouse stomach tissues. Chicken chorioallantoic membrane assays, xenograft tumor models, and human umbilical vein endothelial cell tube formation assays were used for in vivo and in vitro angiogenesis studies. THBS4 was screened from RNA-seq analysis of gastric tissues of BM-MSCs transplanted into H. pylori-infected mice. Results: BM-MSCs can migrate to the site of chronic mucosal injury and promote tumor angiogenesis associated with chronic H. pylori infection. Migration of BM-MSCs to the site of chronic mucosal injury induced the upregulation of THBS4, which was also evident in human gastric cancer and correlated with increased blood vessel formation and worse outcome. The THBS4/integrin α2 axis promoted angiogenesis by facilitating the PI3K/AKT pathway in endothelial cells. Conclusions: Our results revealed a novel proangiogenic effect of BM-MSCs in the chronic H. pylori infection microenvironment, primarily mediated by the THBS4/integrin α2 axis, which activates the PI3K/AKT pathway in endothelial cells and eventually induces the formation of new tumor vessels.
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影响因子：
2.8
作者：
Hou, Yi;Li, Hai;Huo, Wei
通讯作者：
Huo, Wei
影响因子：
1.9
作者：
Lin, Xiandong;Hu, Don;Luo, Xingguang
通讯作者：
Luo, Xingguang
影响因子：
8
作者：
Muppala S;Xiao R;Krukovets I;Verbovetsky D;Yendamuri R;Habib N;Raman P;Plow E;Stenina-Adognravi O
通讯作者：
Stenina-Adognravi O
血小板传播-4的促血管生成特性。
DOI：
10.1161/atvbaha.115.305912
发表时间：
2015-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Muppala S;Frolova E;Xiao R;Krukovets I;Yoon S;Hoppe G;Vasanji A;Plow E;Stenina-Adognravi O
通讯作者：
Stenina-Adognravi O
影响因子：
4.8
作者：
Karar J;Maity A
通讯作者：
Maity A