Collagenase in Human Head and Neck Tumors and Rat Tumors and Fibroblasts in Monolayer Cultures

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Abstract
Invasive tumors must release collagenase to break down the surrounding host connective tissues. The cellular origin of this enzyme is still unclear. We used anticollagenase antibodies to localize collagenase in the human head and neck tumor and rat tumor tissues. Collagenase appeared to be localized in the tumor connective tissue stroma but not in tumor cells. The rat skin fibroblasts in monolayer culture treated with the rat tumor cell-conditioned medium demonstrated marked extranuclear and particulate staining. Fibroblasts without treatment showed no staining. Tumor cells in the culture also showed no staining. Assay of culture media demonstrated that only fibroblasts with the addition of the tumor cell-conditioned medium produced collagenase. These findings suggest the following: 1) collagenase is produced by fibroblasts which are harbored in the connective tissue stroma, but not by tumor cells; 2) cellular interaction between tumor cells and fibroblasts appears to be involved in breakdown of the host connective tissue for tumor cell invasion; and 3) tumor cells release soluble factors which stimulate production of collagenase by fibroblasts.