【Introduction】Several studies showed chemokines contributed to prostate cancer progression. We investigated chemokines in order to reveal the mechanism of prostate cancer activation within microenvironment of prostate cancer bone metastasis.
【Materials and Methods】Androgen-sensitive human prostate cancer cell line (LNCaP), human osteoblast-like cell line (SaOS2), normal bone-derived stromal cells (BDSC), and bone metastatic prostate cancer-derived stromal cells (BmetSC) were used for co-culture assay. We investigated changes in migration and progression of LNCaP by using these co-culture assays (SaOS2, BDSC, BmetSC). We identified proteins which influence variations in phenotype of tumor cells by cytokine array analysis. We used the neutralizing antibody to suppress the function of the secreted protein, and observed the changes in phenotype.
【Results】The migration of LNCaP was increased during co-culture with SaOS2, BDSC, BmetSC, but significantly increased during co-culture with BmetSC. The results of the cytokine array analysis of the conditioned medium from co-culture of BDSC and BmetSC suggested CCL5 could increase LNCaP migration. The migration of LNCaP was increased by CCL5 concentration-dependently. The migration of LNCaP cells was suppressed when CCL5 neutralizing antibody was added during co-culture with BmetSC. Although the migration of LNCaP with silencing androgen receptor by small interfering RNA (siAR) was increased compared with control cells, CCL5 could not increase the migration of LNCaP with siAR any longer.
【conclusions】Elevated CCL5 secretion in bone marrow stromal cells in the bone metastatic site can induce prostate cancer cell migration. Our results are consistent with previous studies showing CCL5 is upstream of AR and can inhibit AR signal.