Carcinogenesis Advance Access published online on June 29, 2007
Carcinogenesis, doi:10.1093/carcin/bgm140
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ECRG2 inhibits cancer cell migration, invasion and metastasis through the down-regulation of uPA/plasmin activity
1 Department of Etiology and Carcinogenesis, Cancer Institute, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing100021, China
2 Department of Laboratory Medicine and Comprehensive Cancer Center, University of California, San Francisco, CA94115, USA
3 The Burnham Institute, La Jolla, CA 92037, USA
* To whom correspondence and reprint requests should be addressed. Tel: 86-10-87788408; Fax: 86-10-67712368, Email: shlu{at}public.bta.net.cn or wjiang{at}burnham.org.
The esophageal cancer related gene2 (ECRG2) is a novel gene which shows sequence similarity to KAZAL-type serine protease inhibitor. In this study, the migration and invasion of PG cancer cells were inhibited by ectopic expression of ECGR2 in vitro, and metastases decreased after injecting PG/pcDNA3.1-ECRG2 cells into the tail veins of nude mice. Control mice were injected compared to those with PG/pcDNA3.1 cells. To test the hypothesis that ECRG2 interacts with proteases and inactivate ECM degradation, binding-affinity and co-immunoprecipitation experiments were performed using serum-free conditioned medium. The results showed that ECRG2 bound to two species of uPA with molecular weights of 55 kDa and 33 kDa. Furthermore, analysis of the uPA/plasmin activity showed that expression of ECRG2 reduced proteolysis of the plasmin substrate D-Val-Phe-Lys-p-nitroanilide, which was seen by a decrease of absorbance at 405nm. Taken together, these results suggested that ECRG2 inhibits aggressiveness of cancer cell, possibly through the down-regulation of uPA/plasmin activity.
Key Words: ECRG2 • protease inhibitor • metastasis • extracellular matrix • urokinase-type plasminogen activator
Received January 29, 2007; revised May 17, 2007; accepted June 16, 2007.
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