Host-mediated effectors of tumor invasion: role of mast cells in matrix degradation

The role of collagenolytic enzymes in tumor invasion and metastasis has been emphasized, but the source of enzyme activity has remained unclear. Degradation of stromal connective tissue is a common feature of invasive neoplasia, and host-tumor cell interactions are probably important for localized collagenolysis. We have examined the role of mast cells in malignant cell invasion using cells derived from the rat mammary adenocarcinoma 13762NF. Histologic studies have shown increased numbers of mast cells at the zone of tumor invasion. Mast cell products and conditioned medium from such cells stimulated the production of collagenolytic enzymes by stromal fibroblasts as well as certain subpopulations of tumor cells in vitro. The tumor cell response to mast cell-mediated stimulation of collagenolysis appears to be related to the metastatic potential of the tumor cell. A subpopulation of host fibroblasts derived from the invading tumor zone was also found to be more responsive to mast cell factors than normal fibroblasts, as judged by collagenase production. Thus the mast cell has the potential to induce collagenolytic activity from both host fibroblasts and tumor cells.