S. Sheng et al., MASPIN ACTS AT THE CELL-MEMBRANE TO INHIBIT INVASION AND MOTILITY OF MAMMARY AND PROSTATIC-CANCER CELLS, Proceedings of the National Academy of Sciences of the United Statesof America, 93(21), 1996, pp. 11669-11674
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podia are withdrawn but ruffling continues.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.