期刊
ONCOTARGETS AND THERAPY
卷 12, 期 -, 页码 4119-4127出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S201121
关键词
renal cancer; tumor microenvironment; cancer-associated fibroblasts; B7-H3; apoptosis; invasion; metastasis
资金
- National Natural Science Foundation of China [81872328]
- Major Project of Natural Science Research of Jiangsu Provincial Department of Education [17KJA310004]
Background: Renal cancer is one of the most common malignancies. However, the mechanisms underlying its development are still ambiguous. B7-H3 has been described as an important tumor antigen in various human tumors. An abnormal high expression of B7-H3 molecules is often observed in tumor cells and tumor stromal cells in the tumor microenvironment. On the basis of the above findings, we hypothesized that cancer-associated fibroblasts (CAFs) clustered in the renal cell microenvironment can survive for a long time with the anti-apoptotic effect of B7-H3, and then secrete cytokines to enhance the malignant behavior of renal cancer cells. Methods: The expression of B7-H3 protein in CAFs was detected in renal cancer tissues. Then, the CAFs cells were stably transfected with shRNA and their expression was silenced to determine the role of B7-H3 in CAFs. Western blot was used to detect the expression of apoptosis-related proteins, hepatocyte growth factor (HGF) protein and stromal cell-derived factor-1 (CXCL12) protein. CAF-NC cells and CAFs-shRNA cells were co-cultured with A498 cells to assess the biological function changes of A498. Results: A group of CAFs were found with B7-H3 expression in renal cancer. B7-H3 can stimulate CAFs to secrete HGF and Cxcl-12, and has strong anti-apoptotic effect on CAFs. We also found that CAFs-NC promotes the proliferation, invasion and migration of A498 cells in vitro and promotes the tumor formation of A498 in vivo. Conclusion: B7-H3(+) CAFs promote the invasion and metastasis in renal cancer.
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