Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis.
The metalloproteinase matrilysin is widely expressed in the epithelial tumor cells of malignant colorectal adenocarcinomas. Approximately 50% of benign adenomas also express low levels of matrilysin that is focally localized. The expression of stromelysin-1, stromelysin-3, and gelatinase A was observed in the stromal component of several carcinomas and was not present in adenomatous tissue. The expression of interstitial collagenase and gelatinase B was observed in occasional adenomas and carcinomas. Stromelysin-2 transcripts were not detectable in any of the samples examined. Tissue inhibitor of metalloproteinase-1 gene expression was widespread and was observed in both epithelial and stromal cells of adenomas and carcinomas. These results indicate that matrilysin gene expression is an early event in colorectal tumorigenesis and that the expression of stromelysin-1, stromelysin-3, and gelatinase A is primarily a late event. The observed gene expression patterns suggest that matrilysin may participate in early events in tumor progression and that multiple members of the metalloproteinase family may work in concert to facilitate late-stage tumor invasion and metastasis.
Newell
K J
KJ
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232.
Witty
J P
JP
Rodgers
W H
WH
Matrisian
L M
LM
D000236:Adenoma / Q000201:enzymology*; D002277:Carcinoma / Q000201:enzymology*; D015179:Colorectal Neoplasms / Q000201:enzymology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7