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Collagenase induction promotes mouse tumorigenesis by two independent pathways
T D Colandrea1, J D'Armiento, K V Kesari
1Department of Biochemistry, University of Medicine and Dentistry-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Molecular Carcinogenesis
|October 6, 2000
Summary
Matrix metalloproteinases, like interstitial collagenase, contribute to tumor formation, not just metastasis. Overexpression of collagenase in mice increased susceptibility to tumorigenesis via multiple pathways.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are implicated in tumor progression and metastasis.
- The specific role of interstitial collagenase in initial tumor formation remains poorly understood.
- Increased MMP presence is observed in human cancers, but their contribution to tumorigenesis is not well defined.
Purpose of the Study:
- To investigate the role of interstitial collagenase in tumor formation and susceptibility.
- To determine if collagenase overexpression contributes to tumorigenesis.
- To explore the molecular mechanisms underlying collagenase's role in tumor development.
Main Methods:
- Utilized wild-type and transgenic mice overexpressing interstitial collagenase in skin epidermis.
- Administered tumor-promoting agents 12-O-tetradecanoylphorbol-13-acetate (TPA) and chrysarobin to induce tumorigenesis.
- Assessed tumor formation, susceptibility, and expression of c-fos.
Main Results:
- Constitutive expression of interstitial collagenase in mouse skin increased susceptibility to TPA- and chrysarobin-induced tumorigenesis.
- Transgenic mice developed tumors at lower doses of TPA compared to wild-type mice.
- Elevated baseline expression of c-fos was observed in collagenase transgenic mice, suggesting a molecular mechanism for increased tumor susceptibility.
Conclusions:
- Interstitial collagenase overexpression contributes to tumorigenesis through both protein kinase C-dependent and -independent pathways.
- The role of MMPs extends beyond metastasis to include initial tumor development.
- MMP deregulation is crucial in tumorigenesis, highlighting their significance in early cancer stages.