The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer.
Several reports have recently documented that CXCR7/RDC1 functions as a chemokine receptor for SDF-1/CXCL12, which regulates a spectrum of normal and pathological processes. In this study, the role of CXCR7/RDC1 in prostate cancer (PCa) was explored. Staining of high density tissue microarrays demonstrates that the levels of CXCR7/RDC1 expression increase as the tumors become more aggressive. In vitro and in vivo studies with PCa cell lines suggest that alterations in CXCR7/RDC1 expression are associated with enhanced adhesive and invasive activities in addition to a survival advantage. In addition, it was observed that CXCR7/RDC1 levels are regulated by CXCR4. Among the potential downstream targets of CXCR7/RDC1 are CD44 and cadherin-11, which are likely to contribute to the invasiveness of PCa cells. CXCR7/RDC1 also regulates the expression of the proangiogenic factors interleukin-8 or vascular endothelial growth factor, which are likely to participate in the regulation of tumor angiogenesis. Finally, we found that signaling by CXCR7/RDC1 activates AKT pathways. Together, these data demonstrate a role for CXCR7/RDC1 in PCa metastasis and progression and suggest potential targets for therapeutic intervention.
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor 48109, USA.
Jianhua
J
Wang
Yusuke
Y
Shiozawa
Jincheng
J
Wang
Yu
Y
Wang
Younghun
Y
Jung
Kenneth J
KJ
Pienta
Rohit
R
Mehra
Robert
R
Loberg
Russell S
RS
Taichman
D001483:Base Sequence; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D054387:Receptors, CXCR / Q000502:physiology*
C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D017931:DNA Primers; D054387:Receptors, CXCR