Proteolytic enzymes in tumor metastasis. II. Collagenase type IV activity in subcellular fractions of cloned tumor cell populations.

Collagenase type IV degradation activity was examined in metastatic and nonmetastatic clones of the Lewis lung carcinoma (3LL) and of the T10 sarcoma. Conditioned media prepared from cells of both tumors grown in vitro contained low degradation activities, whereas conditioned media from organ cultures of the same clones grown as solid tumors in animals exhibited higher degradation activities. Analysis of subcellular fractions of tumor cells showed that collagenase type IV activity was localized mainly in the cytoplasmic fraction. Crude homogenates or detergent lysates manifested low degradation activities. Little activity was associated with purified plasma membrane preparations and endoplasmic reticular fractions. However, addition of plasma membrane to conditioned media and to cytoplasmic fractions reduced the degradation activities of the cytoplasmic fractions. Possibly a factor that inhibits collagenase type IV exists in the cells in a vesicular form. No correlation between degradation activity and metastatic capacity was demonstrated in the models used in this study. Both metastatic and nonmetastatic clones of the same tumor similarly could degrade basement membrane components.