肿瘤相关成纤维细胞通过 TGF-β 信号通路调节前列腺癌细胞的增殖和迁移。

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

机构信息

Department of Urology, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing 210006, Jiangsu, China.

Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, Jiangsu, China.

出版信息

Life Sci. 2019 Oct 15;235:116791. doi: 10.1016/j.lfs.2019.116791. Epub 2019 Aug 26.

DOI:10.1016/j.lfs.2019.116791

PMID:31465732

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.

摘要

目的

目前中国的前列腺癌（PCa）发病率正在上升。癌症相关成纤维细胞（CAFs）作为肿瘤微环境的主要组成部分，对肿瘤的进展至关重要。本研究旨在探讨患者来源的 CAFs 对前列腺癌细胞增殖和迁移的促进作用。

方法

从 PCa 患者的肿瘤组织中分离 CAFs。体外和体内评估 CAFs 对 PC-3 和 LNCaP 细胞增殖和迁移的促进作用。通过 Luminex assay 测量 TGF-β1 的浓度。还评估了 LY2109761 对 CAFs 促进作用的阻断活性。

主要发现

CAFs 可显著促进 PC-3 和 LNCaP 细胞的体外和体内增殖和迁移。与这两种癌细胞系的正常培养基相比，CAFs-CM 中鉴定出 TGF-β1 是一种高度增加的因子。TGF-β 受体抑制剂 LY2109761 可抑制 CAFs 诱导的 PC-3 细胞的细胞增殖和迁移，但不能抑制 LNCaP 细胞。