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Expression of human macrophage metalloelastase (MMP-12) by tumor cells in skin cancer
E Kerkelä1, R Ala-Aho, L Jeskanen
1Department of Dermatology, Helsinki University Central Hospital, Finland.
Abstract:
Matrix metalloproteinases play an essential role in tumor growth and invasion. Different matrix metalloproteinases are often expressed in cancers with distinct patterns. To investigate the role of human macrophage metalloelastase (MMP-12) in epidermal tumors, we studied human macrophage metalloelastase mRNA and protein expression in malignant squamous cell and basal cell carcinomas, and in premalignant Bowen's disease. Human macrophage metalloelastase was detected in 11 of 17 squamous cell carcinomas in epithelial cancer cells, whereas macrophages were positive in 15 of 17 samples. In basal cell carcinomas, human macrophage metalloelastase was more often found in macrophages (seven of 19) than in cancer cells (four of 19). Human macrophage metalloelastase mRNA was also detected in three cell lines derived from squamous cell carcinomas of the head and neck and in transformed HaCaT cells, whereas premalignant tumors and primary keratinocytes were negative for human macrophage metalloelastase mRNA. Western analysis revealed human macrophage metalloelastase protein in squamous cell carcinoma cells. Our results show that human macrophage metalloelastase can be expressed in vivo and in vitro by transformed epithelial cells and indicate that the level of human macrophage metalloelastase expression correlates with epithelial dedifferentiation and histologic aggressiveness.
Insights
Human macrophage metalloelastase (MMP-12) is expressed in skin cancers and correlates with tumor aggressiveness. This enzyme is found in both cancer cells and macrophages, indicating its role in epidermal tumor progression.
Area of Science:
- Oncology
- Cell Biology
- Dermatology
Background:
- Matrix metalloproteinases (MMPs) are crucial for tumor growth and invasion.
- Specific MMPs exhibit distinct expression patterns in various cancers.
- Human macrophage metalloelastase (MMP-12) role in epidermal tumors requires investigation.
Purpose of the Study:
- To examine the expression of human macrophage metalloelastase (MMP-12) in malignant and premalignant epidermal tumors.
- To determine if MMP-12 is expressed by cancer cells or stromal cells in these tumors.
- To correlate MMP-12 expression levels with tumor dedifferentiation and aggressiveness.
Main Methods:
- Analysis of human macrophage metalloelastase mRNA and protein expression.
- Studied samples included squamous cell carcinomas, basal cell carcinomas, and premalignant Bowen's disease.
- Utilized techniques such as Western analysis and detection in cell lines (squamous cell carcinoma-derived and HaCaT cells).
Main Results:
- Human macrophage metalloelastase (MMP-12) was detected in epithelial cancer cells of squamous cell carcinomas (11/17) and macrophages (15/17).
- In basal cell carcinomas, MMP-12 was more prevalent in macrophages (7/19) than cancer cells (4/19).
- MMP-12 mRNA was found in squamous cell carcinoma cell lines and transformed HaCaT cells, but not in premalignant tumors or primary keratinocytes.
Conclusions:
- Human macrophage metalloelastase (MMP-12) is expressed by transformed epithelial cells in vitro and in vivo.
- MMP-12 expression in epidermal tumors correlates with epithelial dedifferentiation.
- The findings suggest MMP-12 plays a role in the progression and aggressiveness of skin cancers.
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