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

Authors Zhang S, Zhou C, Zhang D, Huang Z, Zhang G

Received 10 January 2019

Accepted for publication 5 April 2019

Published 24 May 2019 Volume 2019:12 Pages 4119—4127

DOI https://doi.org/10.2147/OTT.S201121

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Jyoti Bajaj

Peer reviewer comments 3

Editor who approved publication: Dr Takuya Aoki


Shuai Zhang,1,2 Chenchao Zhou,3 Dongze Zhang,1,2 Ziyi Huang,1,2 Guangbo Zhang1,2

1Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University; 2Jiangsu Institute of Jiangsu key Laboratory of Clinical Immunology, Soochow University; 3Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou 216007, People’s Republic of China

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.

Keywords: renal cancer, tumor microenvironment, cancer-associated fibroblasts, B7-H3, apoptosis, invasion, metastasis


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