Involvement of autocrine CXCL12/CXCR4 system in the regulation of ovarian carcinoma cell invasion |
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| Authors: | Miyanishi Nami Suzuki Yukino Simizu Siro Kuwabara Yoshiko Banno Kouji Umezawa Kazuo |
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| Affiliation: | a Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
b Department of Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan |
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| Abstract: | 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. |
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| Keywords: | NF-κB Chemokine MMP Invasion |
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