Cancer-associated fibroblast regulate proliferation and migration of prostate cancer cells through TGF-β signaling pathway

Abstract

Aims: Prostate cancer (PCa) incidence rates are rising in China currently. Cancer-associated fibroblasts (CAFs), as a major component of tumor microenvironment, are crucial for tumor progression. This study was aimed to explore the promotion effect of patient-derived CAFs on the proliferation and migration of prostate cancer cells.

Main methods: CAFs were isolated from tumor tissues of PCa patients. The promotion effect of CAFs on the proliferation and migration of PC-3 and LNCaP cells were evaluated in vitro and in vivo. The concentration of TGF-β1 was measured by Luminex assay. The blocking activity of LY2109761 on the promotion effect of CAFs was also evaluated.

Key findings: CAFs could significantly promote the proliferation and migration of PC-3 and LNCaP cells both in vitro and in vivo. TGF-β1 was identified as a highly increased factor in CAFs-CM compared with the normal culture medium of these two cancer cell lines. TGF-β receptor inhibitor LY2109761 could suppress the CAFs-induced cellular proliferation and migration of PC-3 cells but not LNCaP cells.

Significance: Our study suggested a crucial role for CAFs and TGF-β signaling in the progression of PCa. Zebrafish xenograft model was an ideal animal model for the study of CAFs and cancer cell interaction.

Keywords: CAFs; Prostate cancer; TGF-β; Tumor microenvironment; Zebrafish.