C ‐C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment

Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co‐cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration‐dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C‐C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling.

Elevated CCL5 secretion in bone stromal cells from bone metastatic lesions induced prostate cancer cell migration. The CCL5–CCR5 axis may be a novel therapeutic target and a potential biomarker for prostate cancer.

Source: Cancer Science - February 14, 2018 Category: Cancer & Oncology Authors: Satoko Urata, Kouji Izumi, Kaoru Hiratsuka, Aerken Maolake, Ariunbold Natsagdorj, Kazuyoshi Shigehara, Hiroaki Iwamoto, Suguru Kadomoto, Tomoyuki Makino, Renato Naito, Yoshifumi Kadono, Wen ‐Jye Lin, Guzailinuer Wufuer, Kazutaka Narimoto, Atsushi Mizoka Tags: ORIGINAL ARTICLE Source Type: research