alexa MMP inhibition blocks fibroblast-dependent skin cancer invasion, reduces vascularization and alters VEGF-A and PDGF-BB expression.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular and Genetic Medicine

Author(s): Woenne EC, Lederle W, Zwick S, Palmowski M, Krell H,

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Abstract Tumor invasion requires intense interactions with stromal cells and a profound extracellular matrix remodelling by matrix metalloproteinases (MMPs). Here, we assessed the specific contribution of fibroblasts to tumor invasion, MMPs, tissue inhibitors of MMPs and angiogenesis-related cytokine expression in organotypic cultures of highly malignant HaCaT-ras A-5RT3 cells, with and without MMP inhibition. Collagen degradation, the hallmark of tumor invasion, was dependent on fibroblasts and active MMP-2. Additionally, MMP blockade down-regulated VEGF-A and up-regulated PDGF-BB. These results were paralleled in xenotransplants in vivo, demonstrating strong inhibitory effects of MMP blockade on tumor invasion and vascularization, as shown by the almost complete absence of VEGF-A and MMP-14 and by the decrease in relative blood volume. MMP blockade also increased the fraction of mature vessels, as demonstrated by an increased mean tumor vessel diameter and a higher ratio of Ng2-positive vessels. Thus, this study highlights the importance of targeting the tumor stroma to defeat cancer.
This article was published in Anticancer Res and referenced in Journal of Molecular and Genetic Medicine

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