Adhesion molecules, extracellular matrix, and proteases in prostate carcinoma.
Immunohistochemical studies of prostate carcinoma reveal that most primary carcinomas, including high-grade tumors, are surrounded by a basal lamina composed of laminin, type IV collagen, and entactin. In addition to the expected laminin subchains A, B1, B2, subchains M and S are also found. Tenascin, found around normal glands, is seen in 60% of carcinomas. The basal cells of the normal gland express several integrin alpha 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 base of the cells where they codistribute with the surrounding extracellular matrix. The integrin alpha 6 beta 4 is associated with hemidesmosomal-like structures, as detected by transmission electron microscopy (TEM). In carcinoma, the beta 4 is not observed and the alpha 6 and beta 1 subunits are variably expressed. The integrin expression in carcinoma is diffuse in the cytoplasmic membrane and not restricted to the basal aspects of the cell. In addition, type VII collagen and the BP 180 protein which are associated with hemidesmosomes are lost, although the BP 230, plectin, and HD1 proteins are variably expressed. Using immunohistochemistry and northern analysis we observed three metalloproteinases in prostate carcinoma--matrilysin, gelatinase A, and gelatinase B. Western blotting and zymogram analysis reveal that of these three, only matrilysin appears to be present in its active form. Recent in situ hybridization studies reveal focal expression of the matrilysin mRNA in 25/33 primary carcinomas. Matrilysin also appears to be highly expressed in prostatic ducts and atrophic glands. Expression of the three metalloproteinases is also seen in prostatic intraepithelial neoplasia lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
Nagle
R B
RB
Department of Pathology, University of Arizona Health Sciences Center, Tucson 85724.
Knox
J D
JD
Wolf
C
C
Bowden
G T
GT
Cress
A E
AE
D001344:Autopsy; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000032:analysis*; D010450:Endopeptidases / Q000032:analysis* / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000032:analysis*; D008297:Male; D011467:Prostate / Q000166:cytology / Q000201:enzymology / Q000473:pathology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D016023:Integrins; D012333:RNA, Messenger; D010450:Endopeptidases