Involvement of autocrine CXCL12/CXCR4 system in the regulation of ovarian carcinoma cell invasion.
Ovarian carcinomas are often highly invasive, especially in the peritoneal cavity; however, the mechanism involved in invasion is not yet fully understood. In the present research, we studied the role of NF-κB in the invasiveness of ovarian carcinoma cells by using (-)-DHMEQ, a specific inhibitor of NF-κB. (-)-DHMEQ inhibited invasion in vitro and the expression of CXCL12 and CXCR4. We found that neutralizing antibody against CXCR4 or knockdown of CXCR4 suppressed the invasion. Proteomic analysis revealed that CXCR4-siRNA treatment lowered the secretion of several invasion-related proteins, such as MMP-9 and uPA. These data imply that (-)-DHMEQ suppressed ovarian cell invasion via inhibition of the NF-κB-regulated autocrine system of CXCL12-CXCR4.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Nami
N
Miyanishi
Yukino
Y
Suzuki
Siro
S
Simizu
Yoshiko
Y
Kuwabara
Kouji
K
Banno
Kazuo
K
Umezawa
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019898:Autocrine Communication; D002277:Carcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054852:Small Molecule Libraries
D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D016328:NF-kappa B; D019718:Receptors, CXCR4; D054852:Small Molecule Libraries