Abstract
Matrix metalloproteinase-26 (MMP-26) is a novel member of the MMP family and plays a significant role in the progression of estrogen-dependent malignancies. The present study aimed to investigate the roles of MMP-26 in the growth, invasion and angiogenesis of breast cancer. pcDNA3.1(+)-neo expression plasmids carrying the proMMP-26 coding sequence were used to transfect a breast cancer cell line (MCF-7 cells). The mRNA and protein expression of MMP-26 was determined by RT-PCR, immunofluorescence analysis and flow cytometry. The morphology of transfected cells was observed under an electron microscope. An adherence and spreading assay, Boyden chamber assay, in vivo tumorigenicity assay and in vivo angiogenesis were further modeled to elucidate the roles of MMP-26 in the invasion and angiogenesis of breast cancer. Using electron microscopy, the MMP-26-transfected cells demonstrated increased atypia, including unusual mitotic figures, glucogen pools and special lysosomes in the cytoplasm. The adherence and spreading ability of MMP-26-transfected cells were increased significantly compared with cells in the control group. The Boyden chamber assay demonstrated that the migration and invasion ability of MMP-26-transfected cells was dramatically accelerated compared with the control group, but markedly reduced in the presence of anti-MMP-26 antibody. MMP-26 also increased the malignant phenotype in vivo. The number of vessel branches and the total length of vessels induced by MMP-26-transfected cells were significantly increased compared to those induced by non-transfected cells. The plasmid carrying the proMMP-26 gene was successfully transfected into breast cancer cells. Our results demonstrate that MMP-26 overexpression promotes the growth and invasion of breast cancer cells and induces angiogenesis.