Matrilysin expression in human prostate carcinoma.
The metalloproteinases, a multigene family of metal-requiring enzymes, have been suggested to play a role in tumor invasion and metastasis. Previously, we demonstrated that human primary prostate tumors express higher levels of matrilysin and gelatinase A mRNA than normal prostate does. In the study presented here, we used in situ hybridization and immunohistochemical staining of serial sections of paraffin-embedded primary prostate tumors to compare the sites of matrilysin and gelatinase A expression and protein localization. These results confirmed the epithelial nature of matrilysin expression and protein localization. In contrast, gelatinase A mRNA was localized to the interstitial stroma, whereas the protein was associated with the epithelial tumor cells. In situ hybridization was also used to demonstrate that gelatinase B expression was restricted to macrophages infiltrating the tumors. Proteins isolated from an additional set of frozen tumor specimens were analyzed by western blotting to determine the relative amounts of matrilysin in the active and proenzyme forms. The western analyses demonstrated that in all cases in which matrilysin was detected, at least some of the enzyme was in the active form. These results are discussed with respect to the possible role these enzymes may play in prostate tumor progression.
Knox
J D
JD
Department of Pathology, University of Arizona Health Sciences Center, Tucson, USA.
Wolf
C
C
McDaniel
K
K
Clark
V
V
Loriot
M
M
Bowden
G T
GT
Nagle
R B
RB
D000595:Amino Acid Sequence; D002277:Carcinoma / Q000201:enzymology*; D017364:Collagenases / Q000378:metabolism; D004789:Enzyme Activation; D018093:Gelatinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D020778:Matrix Metalloproteinase 2; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
D010455:Peptides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9