Role of matrix metalloproteinase-9 in progression of mouse skin carcinogenesis

Invasion of malignant tumor cells is required for the formation of metastat ic colonies. Uncontrolled expression of matrix metalloproteinase (MMP)-2 an d MMP-9 is a critical part of the invasive potential of tumor cells and is affected by the balance between the enzymes and the inhibitors secreted by the cell. Here we analyzed the expression and activity of the two gelatinas es (MMP-2 and MMP-9) as well as the expression levels of the tissue inhibit or of metalloproteinase (TIMP2)-, in different stages of carcinogenesis usi ng mouse skin cell lines derived from tumors induced by chemical mutagens. Our results suggested that the expression of MMP-9 was implicated in the pr ogression to spindle cell carcinomas in mouse keratinocytes. MMP-2 levels r emained steady in all cell lines, whereas levels of TIMP-2 were increased i n normal and spindle cells. The AP-1 DNA binding and transcriptional activi ty on the MMP-9 promoter were increased in the malignant cell lines, indica ting the requirement of this binding site for its activation. The results o f this study clearly suggested the important role of MMP-9, but not of MMP- 2, in the metastatic properties of mouse keratinocytes. (C) 2001 Wiley-Liss , Inc.