Related Experiment Videos
Matrix-degrading metalloproteinases in tumor progression
L M Matrisian1, J Wright, K Newell
1Department of Cell Biology, Vanderbilt University, Nashville, TN 37232, USA.
Abstract:
The matrix-degrading metalloproteinases (MMPs) have been implicated in tumor invasion and metastasis. Recently it has become clear that the expression of MMPs in tumors is frequently localized to stromal cells surrounding malignant tumor cells. In the mouse skin model of multi-stage carcinogenesis, the MMP stromelysin is expressed in stromal fibroblast-like cells surrounding benign and malignant squamous cell carcinomas. Conversion of these tumors to highly invasive and metastatic spindle-cell tumors is however, associated with the expression of stromelysin-1 mRNA in the tumor cells themselves. The analysis of MMPs in human colon adenocarcinomas at different stages of tumor progression revealed that matrilysin was the only MMP expressed in the tumor cells, while stromelysin-1 and stromelysin-3 mRNA was detected in stromal cells surrounding malignant tumor cells. Matrilysin mRNA is detected in benign tumors as well as malignant tumor cells, and the relative level and percent of tumors expressing matrilysin correlates with the stage of tumor progression. These results suggest that both stromal and tumor cell metalloproteinases may contribute to tumor invasion and metastasis, and also suggests that MMPs may play a role in earlier events in the tumor progression pathway. A potential role for MMPs in tumor growth is illustrated by results which suggest that the expression of matrilysin in human colon cancer-derived cells increases tumorigenicity following injection into the cecum, and that transgenic mice expressing matrilysin mRNA show a marked proliferative response. MMPs may therefore play multiple roles in tumor progression.
Insights
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.