Work in our laboratory has demostrated the presence of specific collagenolytic activity in invasive human and animal tumors as opposed to noninvasive benign tumors of similar origin. Neutral proteases were also found. We propose to continue the biochemical characterization of components of the collagenolytic system associated with selected invasive human and animal tumors; to correlate the level of the collagenolytic activity with tumor growth and invasion; to determine the distribution of these enzymes and their precursor molecules in the tumor parenchyma and the surrounding stroma; and to investigate the cell origin of the observed increase in enzyme activity. It is proposed that benign tumors which have malignancy potential, may contain precursors or inactive forms of these collagenolytic enzymes which may become activated during transformation by some mechanism to be investigated. The possibility that collagenolytic enzymes of host origin may function in invasive tumor growth is being explored. The interaction between tumor and host tissue and the role of this interaction in the control of the enzyme activity is under investigation. The cell source for the tumor-associated collagenolytic activity is an important question to examine in our work. Preliminary work has shown that fibroblast-like cells derived from VX-2 carcinoma produced high levels of the collagenase activity. Rabbit VX-2 carcinoma will continue to be used as an experimental model system for the study of these mechanisms and to test our hypothesis. It is hoped that with the full characterization of various components of the collagenolytic system and the understanding of the mechanism of control of synthesis and release of these components, tumor growth and invasion may be limited.