Immunocytochemical detection of MMP-3 and -10 expression in hepatocellular carcinomas.
Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling and tumor invasion. The matrix metalloproteinases (MMPs) and their inhibitors have been shown to be critical modulators of ECM composition and are thus crucial in neoplastic cell invasion and metastasis. Expression of MMP-2, -3, -9, -10, and -13 was investigated in human hepatocellular carcinomas (HCCs) employing an indirect alkaline phosphatase conjugated immunocytochemical technique. Evaluation of the results was based on (a) the persent of neoplastically transformed cells/surrounding stroma that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in HCCs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells (++++), and the staining intensity was also the strongest possible (A,B). No immunoreactivity was detected using antibodies directed against MMP-2, -9, and -13.
Bodey
B
B
Department of Pathology, University of Southern California, 8000-1 Canby Avenue, Reseda, CA 91335, USA. Bodey18@aol.com
Bodey
B
B
Siegel
S E
SE
Kaiser
H E
HE
D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D017364:Collagenases / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology*; D053506:Matrix Metalloproteinase 10; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008666:Metalloendopeptidases / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*
D009363:Neoplasm Proteins; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D053506:Matrix Metalloproteinase 10; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9