The anti-apoptotic effect on cancer-associated fibroblasts of B7-H3 molecule enhancing the cell invasion and metastasis in renal cancer

• Published in: OncoTargets and therapy Vol. 12; pp. 4119 - 4127
• Main Authors: Zhang, Shuai, Zhou, Chenchao, Zhang, Dongze, Huang, Ziyi, Zhang, Guangbo
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.05.2019; Dove
• Subjects: Antigens; Apoptosis; Cancer; Cancer cells; Cancer diagnosis; Cancer metastasis; Cytokines; Original Research; Proteins; Tumors; China; cancer-associated fibroblasts; invasion; metastasis; B7-H3; apoptosis; renal cancer; tumor microenvironment
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S201121

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. 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. 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. B7-H3 CAFs promote the invasion and metastasis in renal cancer.