Collagenolytic activity of rabbit V2 carcinoma implanted in the nude mouse

The relative contribution of host cells and tumor cells to the production of collagenase and its regulation during tumorigenesis were studied with the use of a heterologous rabbit tumor-nude mouse host system. The V2 carcinoma, a malignant neoplasm of the New Zealand White rabbit, behaved as a nonmetastasizing, noninvasive tumor when implanted and grown in the inbred Swiss albino nude mouse. The extracts from both tumors contained similar levels of collagenase. Tumor explants also released enzyme into culture medium in both cases, but the rabbit tumor produced approximately 10 times more collagenase than the nude mouse. Freeze-thawing of the explants or treatment with cycloheximide markedly inhibited the appearance of enzyme in the medium from the rabbit tumor but not from the nude mouse tumor. The relative proportions of mouse- and rabbit-derived collagenase in the nude mouse tumor extracts and culture medium were determined with the use of antibodies specific for rabbit V2 tumor and mouse bone collagenases. Approximately 70% of the nude mouse tumor enzyme was derived from the rabbit tumor, and approximately 30% was derived from the mouse host. These findings indicate that the former might represent stored enzyme carried over during tumor transplantation into the nude mouse, whereas the latter might have originated from stimulation of host cells during tumorigenesis.