prinomastat has been researched along with Skin-Neoplasms* in 1 studies
1 other study(ies) available for prinomastat and Skin-Neoplasms
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MMP inhibition blocks fibroblast-dependent skin cancer invasion, reduces vascularization and alters VEGF-A and PDGF-BB expression.
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. Topics: Animals; Becaplermin; Carcinoma, Squamous Cell; Cell Line, Tumor; Collagen; Fibroblasts; Humans; Matrix Metalloproteinases, Secreted; Mice; Mice, Nude; Neoplasm Invasiveness; Organic Chemicals; Piperazines; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Pyrimidines; Skin Neoplasms; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays | 2010 |