title: CXCL16 functions as a novel chemotactic factor for prostate cancer cells in vitro.
abstract: A variety of tumor cells produce chemokines that promote tumor cell proliferation and chemotaxis. We previously reported that CXCL16 production is increased in aggressive prostate cancer cells compared with the less aggressive tumor cells and benign cells as identified in a cytokine antibody array. The functional contribution of CXCL16 in prostate cancer development has not yet been evaluated. Accordingly, mRNA expression of CXCL16 and its receptor, CXCR6, were determined by real-time reverse transcription-PCR in various cancer cell lines, including prostate cancer and tissues obtained from localized and metastatic prostate cancer. Consistent with our finding on CXCL16 protein production by prostate cancer cells, aggressive prostate cancer C4-2B and PC3 cells, as well as bone and liver metastatic tissues, expressed higher levels of both CXCL16 and CXCR6 mRNA compared with the less aggressive prostate cancer LNCaP cells, nonneoplastic PrEC and RWPE-1 cells, and benign prostate tissues, respectively. Furthermore, CXCR6 and CXCL16 protein expressions were examined in tissue specimens by immunohistochemistry. Immunohistochemical examination of CXCR6 expression showed strong epithelial staining that correlated with Gleason score, whereas CXCL16 staining was not. Finally, we found that both interleukin-1beta and tumor necrosis factor alpha significantly induced CXCL16 production by prostate epithelial cells, thereby indicating that inflammatory cytokines may play a role in the CXCL16 induction. CXCL16 was found to promote prostate cancer cell migration and invasion in vitro. Therefore, we concluded that CXCL16 functions, through CXCR6, as a novel chemotactic factor for prostate cancer cells.
authors.affiliation: Department of Medicine, Pittsburgh VA Healthcare System, Research and Development, University of Pittsburgh, Pittsburgh, PA 15240, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
authors.forename: Zhong
authors.initials: Z
authors.lastname: Cai
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Galson
authors.forename: Russell S
authors.initials: RS
authors.lastname: Taichman
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D012333:RNA, Messenger; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha