Overexpression of vacuolar ATPase 16-kDa subunit in 10T1/2 fibroblasts enhances invasion with concomitant induction of matrix metalloproteinase-2

Recent studies show that the vacuolar-type H+-ATPase (V-ATPase) 16 kDa subu nit is expressed on plasma membrane of cancer cells. We hypothesized that V -ATPase 16 kDa subunit is directly involved in cell invasion. In the presen t study we established transfectants overexpressing V-ATPase 16 kDa subunit at the mRNA level, and found that these transfectants showed an enhanced i nvasiveness through matrigel with a concomitant increases in secretion of m atrix metalloproteinase-2. Moreover, antisense oligonucleotides of the V-AT Pase 16 kDa subunit suppressed invasive human A549 cell invasion with conco mitant decreases in secretion of matrix metalloproteinase-2. The results su ggest that the V-ATPase 16 kDa subunit is directly involved in cell invasio n and that matrix metalloproteinase-g is responsible for promoting the inva sion by the V-ATPase 16 kDa subunit. (C) 2000 Academic Press.