In spite of the clinical importance of prostate cancer (PCa) bone metastasis, the precise mechanisms for the directed migration of malignant cells remain unclear. In the present study, the expression of CXCR6 in human PCa and benign prostatic hyperplasia samples, and the expression of CXCL16 in human osseous tissues were determined by immunohistochemistry. It was found that the level of CXCR6 protein expression was elevated in human malignant prostate tumors, and CXCL16 was expressed positively by human osteocytes in vivo. The in vitro experiments further confirmed that the PCa cell lines PC3 and LNCap expressed CXCR6 at both the mRNA and protein levels, and exogenous CXCL16 has the potential to stimulate the invasion of PC3 and LNCap. To further elucidate the role of the CXCL16-CXCR6 axis in PCa progression, we compared the expression of CXCR6 and CXCR4 in human PCa tissues and the effects of CXCL16 and CXCL12 on the in vitro invasion of PC3 and LNCap cells. P rostate cancer is a common neoplasm and the second leading cause of cancer death in American men, and its morbidity has also increased in recent years in China.(1,2) Despite advances in early diagnosis and therapeutics of PCa, metastasis to bone is one of the most severe complications and major causes of mortality of PCa.(3,4) Many factors have been implicated in the process of metastasis, but the precise mechanisms for the directed migration and invasion of malignant cells into selective organs at both the cellular and molecular levels remain unclear.Recent studies indicate that tumor cell migration and metastasis are not random processes; rather, chemokines and chemokine receptors may play important roles in determining the metastatic destination of tumor cells.(5,6) For PCa, most investigations focused on the CXCL12-CXCR4 signaling pathway; (7)(8)(9) however, little is known about the relationship between PCa specific metastasis and other chemokines or chemokine receptors.CXCR6, initially described under the names Bonzo, STRL33 and TYMSTR, is a newly characterized chemokine receptor that until now was described to be expressed selectively by subsets of memory/effector T cells, (10) NK cells, (11) NK T cells,and plasma cells.(13) CXCL16, the sole ligand of CXCR6, is a unique CXC chemokine that exists both in a transmembrane form and a soluble form. (14,15) The interaction between CXCL16 and CXCR6 has been shown to mediate multiple biological activities, including selective trafficking of lymphocyte subsets, cell adhesion, cell survival, chronic inflammation, and antitumor immunity. (16)(17)(18)(19)(20) In particular, human bone marrow plasma cells express CXCR6 selectively, and tissues known to be enriched with plasma cells as well as cultured human bone marrow stromal cells express CXCL16 constitutively, (13) implying the importance of the CXCL16-CXCR6 axis in efficient recruitment to target tissues. Furthermore, it has been found that first-trimester human cytotrophoblasts coexpress CXCL16 and CXCR6 as well as secreted CXCL16, which induces their inva...
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