Cytokines IL-6, IL-10, and CCL5 Secreted by Infiltrating B Cells Promote Cell Migration of Human Prostate Cancer Cell Lines.

OBJECTIVE: The progression of prostate cancer cells to metastasis is supported by their tumor microenvironment. Within this microenvironment, infiltrating immune cells, such as B cells, can be either anti-tumorigenic or pro-tumorigenic. Our preliminary data showed that a higher density of the infiltrating B cells was found near prostate cancer cells in human cancer tissues, as compared to the benign prostate tissue regions, thus suggesting that infiltrating B cells would promote the progression of prostate cancer cells. In this study, we aim to investigate the role of infiltrating B cells in enhancing the migratory ability of human prostate cancer cells. METHODS: We utilized Transwell(®) assays to evaluate the migratory ability of human prostate cancer cells in the presence or absence of B cells, B cell-secreted cytokines, and neutralizing antibodies of B cell-secreted cytokines. We also used Western blot and immunofluorescence staining to evaluate the effects of epithelial-mesenchymal transition on the human prostate cancer cells in response to the B cell cytokines. RESULTS: Our findings showed an increase in migration of human prostate cancer cells in response to co-cultured B cells as well as the identified B cell cytokines: IL-6, IL-10, and CCL5. Neutralization of these cytokines through their specific neutralizing antibodies decreased B cell-induced prostate cancer cell migration. Results from Western blot and immunocytochemistry showed an increase in expression of N-cadherin and Slug, as well as disorganization of ZO-1, amongst the LNCaP cells treated with B cell cytokines. CONCLUSION: These results revealed that infiltrating B cells through their secretion factors enhanced prostate cancer cell migratory ability, which may lead to metastasis.