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

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.

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.

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.

These results revealed that infiltrating B cells through their secretion factors enhanced prostate cancer cell migratory ability, which may lead to metastasis.