Maspin acts at the cell membrane to inhibit invasion and motility of mammary and prostatic cancer cells

Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11669-74. doi: 10.1073/pnas.93.21.11669.

Abstract

Maspin, a novel serine protease inhibitor (serpin), inhibits tumor invasion and metastasis of mammary carcinoma. We show here that recombinant maspin protein blocks the motility of these carcinoma cells in culture over 12 h, as demonstrated by time-lapse video microscopy. Lamellopodia are withdrawn but ruffling continues.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 Boyden chamber assays. In addition, three prostatic cancer cell lines treated with recombinant maspin exhibited similar inhibition of both invasion and motility, suggesting a similar mode of maspin action in these two glandular epithelial cancers. When mammary carcinoma cells were treated with recombinant maspin, the protein was shown by immunostaining to bind specifically to the cell surface, suggesting that maspin activity is membrane associated. When pretreated with antimaspin antibody, maspin loses its inhibitory effects on both invasion and motility. However, 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 invasion and motility by maspin is initially localized to the cell surface.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Breast
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / physiology*
  • Cell Membrane / ultrastructure
  • Cell Movement / drug effects*
  • Epithelium
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Kinetics
  • Male
  • Microscopy, Video
  • Neoplasm Invasiveness*
  • Prostatic Neoplasms / pathology
  • Protein Biosynthesis*
  • Proteins / pharmacology*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / pharmacology
  • Serine Proteinase Inhibitors / biosynthesis
  • Serine Proteinase Inhibitors / pharmacology
  • Serpins / biosynthesis*
  • Serpins / pharmacology*
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Proteins
  • Recombinant Proteins
  • SERPIN-B5
  • Serine Proteinase Inhibitors
  • Serpins