MASPIN ACTS AT THE CELL-MEMBRANE TO INHIBIT INVASION AND MOTILITY OF MAMMARY AND PROSTATIC-CANCER CELLS

Maspin, a novel serine protease inhibitor (serpin), inhibits tumor inv asion and metastasis of mammary carcinoma. We show here that recombina nt maspin protein blocks the motility of these carcinoma cells in cult ure over 12 h, as demonstrated by time-lapse video microscopy. Lamello podia are withdrawn but ruffling continues. Both exogenous recombinant maspin and maspin expressed by tumor transfectants exhibit inhibitory effects on cell motility and cell invasion as shown in modified Boyde n chamber assays. In addition, three prostatic cancer cell lines treat ed with recombinant maspin exhibited similar inhibition of both invasi on and motility, suggesting a similar mode of maspin action in these t wo glandular epithelial cancers. When mammary carcinoma cells were tre ated with recombinant maspin, the protein was shown by immunostaining to bind specifically to the cell surface, suggesting that maspin activ ity is membrane associated. When pretreated with antimaspin antibody, maspin loses its inhibitory effects on both invasion and motility. How ever, when maspin is added to these cells preceding antibody treatment , the activity of maspin is no longer inhibited by subsequent addition of the antibody. It is concluded therefore that the inhibition of inv asion and motility by maspin is initially localized to the cell surfac e.