PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment
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 g...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-05-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317701442 |
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| author | Hui-hui Fan Ling Li Yu-ming Zhang Jie Yang Mao-cheng Li Fang-yin Zeng Fan Deng |
| author_facet | Hui-hui Fan Ling Li Yu-ming Zhang Jie Yang Mao-cheng Li Fang-yin Zeng Fan Deng |
| author_sort | Hui-hui Fan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dde2c6900c984122b481baaea8b1daf7 |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-dde2c6900c984122b481baaea8b1daf72025-08-20T03:57:52ZengSAGE PublishingTumor Biology1423-03802017-05-013910.1177/1010428317701442PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironmentHui-hui Fan0Ling Li1Yu-ming Zhang2Jie Yang3Mao-cheng Li4Fang-yin Zeng5Fan Deng6Department of Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Clinical Laboratory, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Clinical Laboratory, Hospital of Integrated Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Clinical Laboratory, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaTumor-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.https://doi.org/10.1177/1010428317701442 |
| spellingShingle | Hui-hui Fan Ling Li Yu-ming Zhang Jie Yang Mao-cheng Li Fang-yin Zeng Fan Deng PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment Tumor Biology |
| title | PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment |
| title_full | PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment |
| title_fullStr | PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment |
| title_full_unstemmed | PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment |
| title_short | PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment |
| title_sort | pkcζ in prostate cancer cells represses the recruitment and m2 polarization of macrophages in the prostate cancer microenvironment |
| url | https://doi.org/10.1177/1010428317701442 |
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