Specificity and basis of the tissue polypeptide antigen.

TPA is an antigenic molecule which is generally present in human carcinoma tumors. Proliferating cells of tumor or normal origin produce and release TPA. Chemical characterization has shown TPA to be an unbranched peptide chain with an apparent Mr of 4.3 X 10(4) and a frictional ratio of 2.7. The electrophoretic mobility is close to that of beta 2-globulin, the IP is 4.5, and the sedimentation constant is 4.5S. The amino acid sequence of the specific determinant is known and has been synthetically produced. Antibodies to TPA obtained by affinity chromatography with BrCN-activated Sepharose, charged with isolated TPA, are responsible for reactivity with TPA by hemagglutination, radioimmunoassay, immunoelectrophoresis, immunodiffusion in gel, and immunocytochemistry. TPA is nonspecies specific and can be found down to fishes. In cell culture (HeLa) perinuclear formation of TPA is seen early in the S phase. After cell division TPA is externalized leaving the cell free of visible TPA. At this stage a rise of TPA in the cell culture medium is observed. These findings together with extensive clinical studies and use of TPA have led to the hypothesis that TPA is related to proliferative activity in general. Since cancer is based on proliferation of cells, and the genes of cancer cells are not different from those of other cells, it could be helpful to use TPA as a monitor of cell proliferation in the further search for local and general causes of proliferation. This can be done by looking for TPA in body fluids by radioimmunoassay and at the cellular level by immunocytochemistry.