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Matrix metalloproteinase induction in the tumor stroma does not depend on CD147 expression in murine B16 melanoma
Heike Voigt1, Roland Houben, David Schrama
1Department of Dermatology, Julius Maximilians University, Würzburg, Germany. Voigt_H@klinik.uni-wuerzburg.de
Background:
It was conclusively demonstrated that the cell surface glycoprotein CD147 on tumor cells mediates induction of matrix metalloproteinases (MMPs) by stromal cells in humans. However, for murine models such evidence remains elusive.
Methods And Results:
To address the impact of CD147 on MMP expression in the murine B16 melanoma model, we consequently stably knocked down CD147 expression in two B16 sublines. The CD147 knockdown remained stable under in vivo conditions as confirmed by immunohistochemistry. However, no differences in MMP-2, MMP-9 and MT1-MMP expression by stromal and tumor cells were detectable in CD147+ and CD147- tumors. Since the tumor microenvironment is a complex system, involving several cell types, the extracellular matrix and plethora soluble factors, we subsequently studied the role of murine CD147 in vitro. Coculture of melanoma cells with different fibroblast cell lines demonstrated that neither CD147+ nor CD147- B16 tumor cells altered the expression of MMP-2 or MMP-9 by the fibroblasts, although we could confirm the susceptibility of these fibroblasts for MMP induction.
Conclusions:
At least for the murine B16 melanoma model, CD147 expression on tumor cells seems not to be crucial for MMP-2, MMP-9 and MT1-MMP induction on tumor-associated stromal cells.
Insights
In the B16 melanoma model, tumor cell CD147 (Cluster of Differentiation 147) did not significantly impact matrix metalloproteinase (MMP) induction in stromal cells. This suggests CD147 is not crucial for MMP regulation in this specific murine cancer model.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- CD147 (Cluster of Differentiation 147) on human tumor cells induces matrix metalloproteinases (MMPs) by stromal cells.
- Evidence for this mechanism in murine models is lacking.
Purpose of the Study:
- To investigate the role of CD147 in MMP induction within the murine B16 melanoma model.
- To determine if CD147 expression on tumor cells influences MMP expression by associated stromal cells.
Main Methods:
- Stable knockdown of CD147 in B16 melanoma cell lines.
- In vivo validation of CD147 knockdown using immunohistochemistry.
- In vitro coculture experiments with melanoma cells and fibroblast cell lines to assess MMP expression.
Main Results:
- CD147 knockdown remained stable in vivo.
- No significant differences in MMP-2, MMP-9, or MT1-MMP expression were observed between CD147-positive and CD147-knockdown tumors.
- In vitro, B16 melanoma cells (both CD147-positive and knockdown) did not alter MMP-2 or MMP-9 expression by fibroblasts.
Conclusions:
- CD147 expression on tumor cells is not critical for the induction of MMP-2, MMP-9, and MT1-MMP in tumor-associated stromal cells within the murine B16 melanoma model.
- These findings contrast with observations in human systems, highlighting model-specific differences.
