RESEARCH ARTICLE The Oncogenic Response to MiR-335 Is Associated with Cell Surface Expression of Membrane-Type 1 Matrix Metalloproteinase (MT1-MMP) Activity

MicroRNAmiR-335 has been reported to have both tumor suppressor and oncogenic activi-ties. In order to determine possible tissue and cell type differences in response to miR-335, we examined the effect of miR-335 on cell expression of MT1-MMP, a proteinase commonly expressed in tumors and associated with cell proliferation and migration. miR-335 increased cell surface expression of MT1-MMP in fibrosarcoma HT-1080 and benign pros-tate BPH-1 cells, but not in prostate LNCaP or breast MCF-7 tumor cells. miR-335 stimu-lated proliferation and cell migration in a wound healing in vitro assay in HT-1080, BPH-1, and U87 glioblastoma cells, cells which demonstrated significant cell surface expression of MT1-MMP. In contrast, miR-335 did not affect proliferation or migration in cells without a prominent plasma membrane associated MT1-MMP activity. Our data suggest that differ-ences in response to miR-335 by tumor cells may lie in part in the mechanism of regulation of MT1-MMP production