[The effect of recombinant tissue inhibitor of metalloproteinase-3 (TIMP-3) on tumor growth and metastases].
OBJECTIVE
To investigate the anti-cancer effect of tissue inhibitor of metalloproteinase-3 (TIMP-3) and its mechanism of action.


METHODS
Recombinant TIMP-3(rTIMP-3) was prepared and used to study its effect on tumor growth and metastases in mice, and its effect on angiogenesis in chicken embryo allantoic membrane (CAM).


RESULTS
rTIMP-3 was able to inhibit growth of subcutaneously implanted S180 sarcoma and hepatic carcinoma H22 in a dose-dependent manner. When the rTIMP-3 was given i.p. at a daily dose of 20 mg/kg body weight for 10 days, the growth of S180 sarcoma and H22 carcinoma was inhibited by 63.2% and 73.4%, respectively. The metastases of i.v. injected Lewis lung carcinoma(3LLC) was also suppressed by rTIMP-3, with an inhibition rate of 59.8%. rTIMP-3 was found to significantly inhibit angiogenesis in CAM assay.


CONCLUSIONS
rTIMP-3 has anti-cancer activity, and the mechanism of action might be associated with its inhibition on extracellular matrix degradation and anti-angiogenesis.
Sun
J
J
Shanghai Institute of Biochemistry, Chinese Academy of Sciences.
Zhang
C
C
Yin
X
X
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000556:secondary; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011994:Recombinant Proteins / Q000627:therapeutic use; D012510:Sarcoma 180 / Q000188:drug therapy*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D019717:Tissue Inhibitor of Metalloproteinase-3