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Modulation of Matrilysin Levels in Colon Carcinoma Cell Lines Affects Tumorigenicity in Vivo¹

Department of Cell Biology, Vanderbilt University Medical School, Nashville, Tennessee 37232-2175 [J. P. W., S. M., K. N., L. M. M.], and Syntex Research, Palo Alto, California 94303 [P. C., M. N., R. T.]

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.

¹ This research was supported by NIH Grant CA60867. K. N. was supported by a postdoctoral fellowship from the National Cancer Institute of Canada.

² Present address: Department of Biology, Dublin City University, Glasnevin, Dublin 9, Ireland.

³ Present address: McMaster University, Hamilton, Ontario, Canada L8S 4K1.

⁴ Present address: Affymax Research Institute, 3410 Central Expressway, Santa Clara, CA 95051.

⁵ Present address: Glycomed Inc., 860 Atlantic Avenue, Alameda, CA 94501.

⁶ To whom requests for reprints should be addressed, at Department of Cell Biology, Vanderbilt University Medical Center, C-2310 Medical Center North, Nashville, TN 37232-2175.

Received 4/ 8/94. Accepted 6/27/94.

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