Fibroblasts associated with prostate cancer promote monocyte migration by secreting c-c motif chemokine ligand 15
SHAO Yi,SONG Sheng-ju,HAN Rui-fa
Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin300211, China
Abstract:
Objective To investigate the expression and origin of c-c motif chemokine ligand 15(CCL15) in the microenvironment of prostate cancer, as well as its impact on monocyte migration ability. Methods CCL15 immunofluorescence staining was performed on normal prostate tissue and prostate cancer tissue, and immunohistochemical and immunofluorescence double staining experiments were used to explore the main source cells of CCL15. Isolate fibroblasts from fresh normal prostate tissue and prostate cancer tissue and perform primary culture. Detect fibroblasts through QPCR, WB, and ELISA experiments expression of α-SMA, FAP, Vimentin, and CCL15. Using lentivirus transfection to knock down CCL15, investigate the effect of knocking down CCL15 on the migration ability of monocytes in fibroblast conditioned medium. Perform multi-color immunofluorescence staining to detect the positional relationship between CCL15 and M2 macrophages in prostate cancer tissue. Results The expression of CCL15 in prostate cancer tissue is significantly higher than that in normal tissue, and it mainly comes from its expression of α-SMA. Compared with normal fibroblasts, prostate cancer associated fibroblasts significantly enhance their ability to secrete CCL15. After knocking down CCL15, the secretion of CCL15 by cancer associated fibroblast was significantly reduced, weakening the migration ability of monocytes. In prostate cancer tissue, there are more M2 macrophages in the high expression region of CCL15. Conclusion CAF promotes monocyte migration and increases M2 macrophage infiltration in the prostate cancer microenvironment by secreting CCL15.
