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
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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]