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Matrix-degrading metalloproteinases in tumor progression
L M Matrisian1, J Wright, K Newell
1Department of Cell Biology, Vanderbilt University, Nashville, TN 37232, USA.
Princess Takamatsu Symposia
|January 1, 1994
Summary
Matrix-degrading metalloproteinases (MMPs) in both tumor and stromal cells contribute to cancer invasion and metastasis. Matrilysin expression correlates with tumor progression and increases tumorigenicity, suggesting MMPs play multiple roles in cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Matrix-degrading metalloproteinases (MMPs) are implicated in tumor invasion and metastasis.
- MMP expression is often localized to stromal cells surrounding tumor cells.
Purpose of the Study:
- To investigate the roles of MMPs in different stages of tumor progression, invasion, and metastasis.
- To determine the specific MMPs expressed by tumor cells versus stromal cells in various cancer models.
Main Methods:
- Analysis of MMP expression (mRNA) in mouse skin carcinogenesis models.
- Examination of MMPs in human colon adenocarcinomas at different stages of progression.
- Assessment of matrilysin's effect on tumorigenicity in vivo and cell proliferation in transgenic mice.
Main Results:
- Stromelysin is expressed in stromal cells in mouse skin tumors; stromelysin-1 mRNA appears in tumor cells during conversion to invasive tumors.
- In human colon cancer, matrilysin is found in tumor cells, while stromelysin-1 and -3 are in stromal cells.
- Matrilysin expression in tumor cells correlates with cancer stage and increases tumorigenicity and proliferation.
Conclusions:
- Both tumor and stromal cell-derived MMPs likely contribute to cancer invasion and metastasis.
- MMPs, particularly matrilysin, may play roles in early tumor progression events and enhance tumor growth.
- MMPs have multifaceted roles in tumor development, from initiation to metastasis.