Expression of type‐IV collagenases in human tumor cell lines that can form liver colonies in chick embryos

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Abstract
Chick embryo has been used as a model system for evaluating the metastatic potential of tumor cells. We have previously demonstrated that expression of the tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐I) gene can suppress liver colonization of tumor cells in chick embryo, probably by inhibiting the activity of matrix metalloproteinases (MMP) produced by tumor cells. In an attempt to identify MMP associated with liver colonization, we examined 24 human tumor cell lines for their potential to form metastatic colonies in chick‐embryo liver after the cells had been inoculated into the chorioallantoic membrane (CAM) vein. We compared the results with the mRNA expression of MMP (MMP‐1, MMP‐2, MMP‐3, MMP‐9) studied previously. Three of 8 cell lines from mesenchymal tumors (fibrosarcoma HT1080, osteosarcomas SK‐ES and MNNG/ HOS) and 2 of 16 cell lines from epithelial tumors (gastric carcinoma KKLS and bladder carcinoma T24) proliferated in the livers. MMP‐2 and MMP‐9 were the enzymes whose transcripts were more frequently expressed in these 5 metastatic cell lines (MMP‐1; 2/5, MMP‐2; 4/5, MMP‐3; 0/5, MMP‐9; 3/5), but other cell lines that did not form liver colonies expressed the transcripts at lower frequency (MMP‐2; 7/19, MMP‐9; 3/19). Although either or both MMP‐2 and MMP‐9 transcripts were expressed in 4 of the 5 metastatic cell lines, they were undetectable in T24 cells. However, induced expression of both enzymes was detected by immunostaining in the T24 cells colonized in the liver. Thus, type‐IV collagenases expressed by tumor cells may play a role in facilitating colonization in chick embryos.