Interstitial collagenases as markers of tumor progression

Degradation of the extracellular matrix: is the sine qua non of tumor invas ion and metastasis. Most of this degradation is mediated by matrix metallop roteinases (MMPs), a family of enzymes that, collectively, degrades the ext racellular matrix. Although the basement membrane-degrading enzymes, MMP-2 and MMP-9, have been given considerable attention for their roles In invasi on and metastasis, the interstitial collagenases, a subfamily of MMPs that cleaves the stromal collagens types I and III, have received relatively lit tle recognition for their part in these processes. This subfamily is compri sed of collagenase 1 (MMP-1), collagenase 3 (MMP-13), and the MT-MMPs, memb rane-bound MMPs, and numerous reports over the last several Sears document the expression of these MMPs in a wide variety of advancing tumors. Of part icular interest is a single nucleotide polymorphism in the MMP-1 promoter t hat increases the transcription of this gene acid that is associated with m elanoma and with ovarian and endometrial cancers. The collagenases can medi ate tumor invasion through several mechanisms, which include constitutive p roduction of enzyme by the tumor cells, induction of collagenase production in the neighboring stromal cells, and interactions between tumor/stromal c ells to induce collagenase production by one or both cell types, Thus, evid ence indicates that elevated expression of the interstitial collagenases is associated with a poor prognosis in a variety of cancers, and therefore, t hese MMPs can serve as a marker of tumor progression.