Up-regulation of TIMP-1 expression in B16-F10 melanoma cells suppresses their metastatic ability in chick embryo.

Clonal B16-F10 cell lines with increased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) have been generated by transfection with a TIMP-1-containing expression vector. The parental B16-F10 and control 1-2 cells, and two TIMP-1 up-regulated clones (2-10, 6-5), were studied for their growth characteristics in tissue culture and their experimental metastatic ability in the chick embryo. Both of the TIMP-1 up-regulated clones showed slower in vitro growth and had lower saturation densities. Both clones were also less metastatic following intravenous injection into chick embryos, and formed significantly fewer metastatic tumors in the chorioallantoic membrane and in the liver than did parental B16-F10 and control cells. Furthermore, the size of tumors formed by TIMP-1 up-regulated cells was significantly reduced in comparison to the tumors produced by B16-F10 or control cells. Our results show that malignant cell lines genetically modified to express increased levels of TIMP-1 exhibit a suppressed experimental metastatic ability in vivo. We propose that TIMP-1 suppresses metastatic ability by decreasing both invasive and growth abilities.