ADHESION MOLECULES, EXTRACELLULAR-MATRIX, AND PROTEASES IN PROSTATE CARCINOMA

Immunohistochemical studies of prostate carcinoma reveal that most pri mary carcinomas, including high-grade tumors, are surrounded by a basa l lamina composed of laminin, type IV collagen, and entactin. In addit ion to the expected laminin subchains A, B-1, B-2, subchains M and S a re also found. Tenascin, found around normal glands, is seen in 60%, o f carcinomas. The basal cells of the normal gland express several inte grin cr units including alpha(2,3,4,5,6,) and v. Both beta(1) and beta (4) subunits are observed. These integrin units are polarized at the b ase of the cells where they codistribute with the surrounding extracel lular matrix. The integrin alpha(6) beta(4) is associated with hemides mosomal-Like structures, as detected by transmission electron microsco py (TEM). In carcinoma, the beta(4) is not observed and the alpha(6) a nd beta(1) subunits are variably expressed. The integrin expression in carcinoma is diffuse in the cytoplasmic membrane and not restricted t o the basal aspects of the cell. In addition, type VII collagen and th e BP 180 protein which are associated with hemidesmosomes are lost, al though the BP 230, plectin, and HD1 proteins are variably expressed. U sing immunohistochemistry and northern analysis we obser ed three meta lloproteinases in prostate carcinoma-matrilysin, gelatinase A, and gel atinase B. Western blotting and zymogram analysis reveal that of these three, only matrilysin appears to be present in its active form. Rece nt in situ hybridization studies reveal focal expression of the matril ysin mRNA in 25/33 primary carcinomas. Matrilysin also appears to be h ighly expressed in prostatic ducts and atrophic glands. Expression of the three metalloproteinases is also seen in prostatic intraepithelial neoplasia lesions. The lysosomal protease cathepsin D is focally expr essed in 39/78 carcinomas. This expression shows a tendency to increas e with histologic grade (p = 0.055), and is related to pathologic stag e (p = 0.031). These proteases most likely participate in a cascade of enzymatic reactions which include the plasminogen activator, urokinas e. During prostate tumor progression, alterations occur in the extrace llular matrix, cellular surface integrins, and protease expression, su ggesting a dynamic remodeling of tissue. Further analysis of these alt erations are ongoing in an effort to determine the value of these fact ors as prognostic indicators of the disease. (C) 1994 Wiley-Liss, Inc.