Our research focuses on the molecular and cellular mechanisms by which the collagenases, the only enzymes able to degrade collagen at neutral pH, facilitate the invasive and metastatic behavior of tumor cells. In most normal cells, constitutive expression of the collagenases is low, but increases in response to cytokines such as Interleukin-1 and Tumor Necrosis Factor. We are genotyping individuals with cancers to assess their genotype for this SNP, and are using a quantitiative invasion assay to monitor the invasion of tumor cells through interstitial collagen. Finally, we are examining the ability of novel therapeutic agents to suppress collagenase and thereby to also suppress invasion and metastasis. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription.
Invasion is inhibited by all-trans retinoic acid.