Matrix metalloproteinase-11 overexpressed in lobular carcinoma cells of the breast promotes anoikis resistance

The purpose of the present study was to examine the pathobiological properties of a matrix metalloproteinase, MMP-11 (also known as stromelysin-3), in the carcinogenesis of lobular carcinoma of the breast. Immunohistochemical staining demonstrated immunoreactivity with specific antibody to MMP-11 in 16 of 30 lobular carcinoma cells, but not in the non-cancerous terminal duct lobular unit. In positive cases, both noninvasive and invasive cancer cells exhibited immunoreactivity with anti-MMP-11 antibody; however, the staining patterns in noninvasive and invasive foci were distinct. In the noninvasive foci, immunoreactivity was observed in the cytoplasm beneath the plasma membrane, whereas immunoreactivity was found in all of the cytoplasm of infiltrating lobular carcinoma cells. Enforced expression of MMP-11 in the cultured lobular carcinoma MDA-MB-330 cells did not affect cell growth or Matrigel invasion activity. By contrast, overexpression of MMP-11 significantly increased resistance to anoikis, a programmed cell death triggered by a lack of proper cell matrix interaction, as evidenced by decrease in annexin V-positive cells and apoptotic DNA ladders. The present findings indicate that MMP-11 is overexpressed in many lobular carcinoma cells and that it may play a role in lobular carcinogenesis through increasing resistance to anoikis.