A wide variety of neoplastically transformed rodent and human fibroblast and epithelial cells secrete a transformation-dependent phosphoprotein with a molecular weight of approximately 62,000. Tumorigenic cells exhibit a 10-fold or greater increase in secretion of this phosphoprotein as compared to their normal or nontumorigenic counterparts and this increase is independent of the transforming agent. Cancer patients with carcinomas of the liver, pancreas, colon, breast, prostate, ovary, or lung have all been shown to have markedly elevated plasma levels of what is almost certainly this same protein. A major goal of the proposed research is to determine the biological function of this phosphoprotein and relate this function to the biology of tumor growth. In particular, the phosphoprotein, which is closely relate to an as of yet unidentified normal plasma protein, will be subjected to sequence analysis in order to assess its potential relatedness to any of the previously sequenced proteins. Sequence information will be used to guide efforts to identify biological or enzymatic activity associated with the phosphoprotein. In addition, studies will be performed to further characterize the apparently specific interaction of the phosphoprotein with the surfaces of various cell types. Another major goal of the project is to further assess the possibility that the phosphoprotein is a useful marker for monitoring tumor progression or reacurrence, and effectiveness of therapy. In order to make this assessment, significant numbers of serum samples from patients with a variety of neoplastic and non-neoplastic conditions will be analyzed. In addition, patients with malignancies will be followed during the course of therapy to determine if phosphoprotein blood levels correlate with apparent tumor burden.
