Many human tumors are associated with a fibrotic response, termed the desmoplastic reaction. The most profound reaction is elicited by human breast tumors. It is not known whether this connective tissue reaction is the product of fibroblasts in the invaded host tissue, is synthesized by the malignant epithelial cells of the tumor, or is perhaps dependent on an interaction between the two cell types. This proposal attempts to answer these questions, and to determine the molecular basis of the response in tissue culture. Established lines of human breast tumor cells obtained from malignant effusions from women with disseminated disease will be examined for their ability to elaborate collagen and collagenase into tissue culture medium. Normal human skin fibroblasts will also be examined for their ability to synthesize collagen and collagenase. The effects of conditioned media as well as the effect of cells grown on a preformed extracellular matrix will be examined. In preliminary studies, a polypeptide factor has been identified which underlies this desmoplastic reaction. The immediate goal of the current studies will be to isolate and purify this peptide, and to prepare an antibody which will permit development of a radioimmune assay. This may provide a clinical marker for identifying patients with occult breast carcinomas.