Tumor-associated macrophages are key regulators of the complex interplay between
tumor and tumor microenvironment. M2 Macrophages, one type of tumor-associated macrophages, are involved in
prostate cancer growth and progression.
Protein kinase C zeta has been shown to suppress
prostate cancer cell growth, invasion, and
metastasis as a
tumor suppressor; however, its role in chemotaxis and activation of tumor-associated macrophages remains unclear. Here, we investigated the role of
protein kinase C zeta of
prostate cancer cells in regulation of macrophage chemotaxis and M2 phenotype activation. Immunohistochemistry was performed to analyze the expression of
protein kinase C zeta and the number of CD206+ M2 macrophages in human prostate tissue. Macrophage chemotaxis and polarization were examined using Transwell migration assays and a co-culture system. Quantitative real-time polymerase chain reaction, western blotting, and
enzyme-linked
immunosorbent assay were used to detect M2 markers,
protein kinase C zeta,
interleukin-4, and
interleukin-10 expression. We found the expression of
protein kinase C zeta increased in
prostate cancer tissues, especially in the early stage, and was negatively associated with
tumor grade and the number of CD206+ macrophages. Inhibition of
protein kinase C zeta expression in
prostate cancer cells promoted chemotaxis of peripheral macrophages and acquisition of M2 phenotypic features. These results were further supported by the finding that silencing of endogenous
protein kinase C zeta promoted the expression of
prostate cancer cell-derived
interleukin-4 and
interleukin-10. These results suggest that
protein kinase C zeta plays an important role in reducing infiltration of tumor-associated macrophages and activation of a pro-
tumor M2 phenotype, which may constitute an important mechanism by which
protein kinase C zeta represses
cancer progression.