ECRG2 inhibits cancer cell migration, invasion and metastasis through the down-regulation of uPA/plasmin activity.
The esophageal cancer-related gene 2 (ECRG2) is a novel gene that 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 ECRG2 in vitro, and metastases decreased after injecting PG/pcDNA3.1-ECRG2 cells into the tail veins of nude mice. Control mice were injected with PG/pcDNA3.1 cells. To test the hypothesis that ECRG2 interacts with proteases and inactivates extracellular matrix degradation, binding affinity and co-immunoprecipitation experiments were performed using serum-free conditioned medium. The results showed that ECRG2 bound to two species of urokinase-type plasminogen activator (uPA) with molecular weights of 55 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 405 nm. Taken together, these results suggested that ECRG2 inhibits aggressiveness of cancer cell, possibly through the down-regulation of uPA/plasmin activity.
Huang
Ge
G
Department of Etiology and Carcinogenesis, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
Hu
Zhi
Z
Li
Meining
M
Cui
Yongping
Y
Li
Yuanyuan
Y
Guo
Liping
L
Jiang
Wei
W
Lu
Shih Hsin
SH
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018076:DNA, Complementary; D015536:Down-Regulation / Q000502:physiology*; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D053491:Proteinase Inhibitory Proteins, Secretory; D000074162:Serine Peptidase Inhibitors, Kazal Type; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D018076:DNA, Complementary; D053491:Proteinase Inhibitory Proteins, Secretory; C473799:SPINK7 protein, human; D000074162:Serine Peptidase Inhibitors, Kazal Type; D025521:Tumor Suppressor Proteins; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases