Tumor-associated macrophages promote prostate cancer migration through activation of the CCL22-CCR4 axis

Abstract

Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2–CCR2 axis. The CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was reported to be associated with lung metastasis. The aim of this study was to elucidate the role of CCR2 and CCR4 in prostate cancer progression. CCR2 and CCR4 were expressed in human prostate cancer cell lines and prostate cancer tissues. In vitro co-culture of prostate cancer cells and macrophages resulted in increased CCL2 and CCR2 levels in prostate cancer cells. The addition of CCL2 induced CCL22 and CCR4 production in prostate cancer cells. The migration and invasion of prostate cancer cells via enhanced phosphorylation of Akt were promoted by CCL17 and CCL22. CCR4 may be a potential candidate for molecular-targeted therapy.

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

“…Co‐cultures of SaOS‐2 cells and bone stromal cells with prostate cancer cells found that both cell types induced the migration of AR‐positive cancer cells. Bone tissue is rich in cytokines that are known to affect the behavior of cancer cells . CCL5 was consistently secreted by BDSC and BmetSC and, as previously shown, directly increased prostate cancer cell migration but not proliferation.…”

“…For example, C‐C motif ligand 2 (CCL2) is present in the microenvironment of many cancers and upregulated in prostate cancer cells . We previously reported that bone stromal cells and SaOS‐2 osteoblast‐like cells promoted prostate cancer metastasis through activation of transforming growth factor (TGF)‐β1, and that CCL2, CCL4 and CCL22 were associated with prostate cancer progression . Upregulation of CCL5, a high‐affinity ligand of CCR5, can increase the aggressive potential of breast cancer cells and increase the invasiveness of prostate cancer cells .…”

CCL2 induces resistance to the antiproliferative effect of cabazitaxel in prostate cancer cells

“…CCL2 was shown to attract macrophages, and these macrophages transform to tumor‐associated macrophages in the tumor microenvironment and contribute to cancer progression . Tumor‐associated macrophages stimulate prostate cancer cells to secrete CCL17 and CCL22, which increase their migration ability via an autocrine mechanism . The expression level of CCR4 (a common receptor of CCL17 and CCL22) was shown to be associated with the expression level of CCR2 in prostate cancer tissues.…”

“…The expression level of CCR4 (a common receptor of CCL17 and CCL22) was shown to be associated with the expression level of CCR2 in prostate cancer tissues. In addition, prostate cancer tissues of patients with locally advanced or metastatic cancer show a high expression of CCR4 . In addition, CCL17 and CCL22 were shown to activate regulatory T‐lymphocytes that inhibit the anticancer cell activity of cytotoxic T‐lymphocytes .…”

CCL17‐CCR4 axis promotes metastasis via ERK/MMP13 pathway in bladder cancer

“…Olkhanud et al showed that the process of breast cancer lung metastasis was correlated with CCR4 expression and regulatory T cells. Moreover, CCL17/CCL22‐CCR4 axis played an important role in migration and invasion in prostate cancer . Gastric carcinoma patients with higher CCR4 expression have a significantly poorer prognosis than patients with lower CCR4 expression .…”