Objective: To study the function of MT1-MMP in tumor angiogenesis and elucidate the possible way of action that MT1-MMP contributes to angiogenesis.
Methods: MT1-MMP was transfected into human breast carcinoma cell line MCF-7 cells. Semi-quantitative RT-PCR and immunofluorescence staining were employed to detect the expression of VEGF in the transfected and non-transfected MCF-7 cells. Tumor growth, microvessel density and expression of VEGF in nude mice were detected through in vivo tumorigenicity assay.
Results: In MT1-MMP stable transfected MCF-7 cells, mRNA expression of VEGF(189), VEGF(165), and VEGF(121) and immunofluorescence intensity were significantly elevated (P < 0.001). In vivo tumorigenicity assay in the nude mice showed that MT1-MMP promoted tumor growth. The MVD in the MT1-MMP-transfected cells-transplanted tumor tissue was significantly elevated (P < 0.05). Immunohistochemical assay showed that there was a strong immunostaining of VEGF in those tumor tissues.
Conclusion: MT1-MMP can induce tumor angiogenesis through up-regulation of VEGF expression. This function of MT1-MMP may open a new approach for clinical anti-tumor research and anti-tumor drug development.