Modulation of matrilysin levels in colon carcinoma cell lines affects tumorigenicity in vivo.
The expression of the metalloproteinase matrilysin in the human colon carcinoma cell lines SW480 and SW620 correlates with the ability of the SW620 cells to invade an artificial basement membrane in vitro and metastasize to the liver following injection into the cecum of nude mice in vivo. Transfection of either wild-type or activated forms of matrilysin into the SW480 cells, which do not express endogenous matrilysin, did not reproducibly increase in vitro invasion but increased the tumorigenicity of the cells when injected into the cecum of nude mice. Antisense reduction of matrilysin levels decreased the tumorigenicity of the SW620 cells and subsequent metastasis to the liver. These results suggest that matrilysin gene expression by colon adenocarcinoma cells is not sufficient for tumor invasion and metastasis but contributes to the tumorigenicity and progression of colorectal tumors.
Witty
J P
JP
Department of Cell Biology, Vanderbilt University Medical School, Nashville, Tennessee 37232-2175.
McDonnell
S
S
Newell
K J
KJ
Cannon
P
P
Navre
M
M
Tressler
R J
RJ
Matrisian
L M
LM
D000008:Abdominal Neoplasms / Q000209:etiology / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D002430:Cecal Neoplasms / Q000209:etiology / Q000473:pathology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D015536:Down-Regulation; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D017354:Point Mutation; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases; D014162:Transfection; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7