title: SDF-1/CXCR7 axis enhances ovarian cancer cell invasion by MMP-9 expression through p38 MAPK pathway.
abstract: Ovarian cancer is an aggressive gynecological malignancy with high metastatic potential. Recently, the CXC receptor (CXCR7) has been identified as a new receptor for stromal-derived factor-1 (SDF-1), and exerts important roles in cancer development. However, its effect on ovarian cancer and the underlying mechanism remain unknown. In this study, we detected abundant CXCR7 expression in ovarian cancer tissues and cells. Moreover, SDF-1 induced dramatically upregulation of CXCR7 mRNA and protein levels, indicating that the SDF-1/CXCR7 axis existed in ovarian cancer. Further analysis confirmed that SDF-1 enhanced cell adhesion and subsequent invasion, which were significantly attenuated when pretreated with CXCR7 small interference RNA (siRNA), indicating the critical function of SDF-1/CXCR7 in cell invasion. Further mechanistic analysis indicated that SDF-1/CXCR7 enhanced cell invasion by matrix metalloproteinase (MMP)-9, as pretreatment with MMP-9 siRNA significantly abrogated a number of invading cells. Additionally, SDF-1/CXCR7 induced phosphorylation of the p38 MAPK pathway, which was accounted for MMP-9 expression as preconditioning with the p38 MAPK inhibitor SB203580 obviously decreased MMP-9 expression. Together, our data implied that SDF-1/CXCR7 enhanced ovarian cancer cell invasion by MMP-9 expression through the p38 MAPK pathway. Thus, these findings confirmed the critical role of SDF-1/CXCR7 during the pathological processes of ovarian cancer and supported its potential targets for further development of antiovarian cancer therapy.
authors.affiliation: 1 Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University , Xi'an, China .
authors.forename: Yuecheng
authors.initials: Y
authors.lastname: Yu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Baoyao
authors.initials: B
authors.lastname: Xue
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.forename: Kan
authors.initials: K
authors.lastname: Huang
authors.forename: Junli
authors.initials: J
authors.lastname: Ge
authors.forename: Hongju
authors.initials: H
authors.lastname: Zhang
authors.forename: Biliang
authors.initials: B
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000556:secondary; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D054387:Receptors, CXCR / Q000378:metabolism*; D055815:Young Adult
chemical_list: C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9