Home LiteratureArticle Details
PMID: 8876194 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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 States of America ·Vol. 93 ·No. 21 ·1996-10-15 ·Pages 11669-74

Sheng S, Carey J, Seftor EA, Dias L, Hendrix MJ, Sager R

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 Lamellopodia are withdrawn but ruffling continues.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.

MeSH Terms
Antineoplastic Agents/pharmacology Breast Breast Neoplasms/pathology Cell Line Cell Membrane/drug effects,physiology,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,pharmacology Serine Proteinase Inhibitors/biosynthesis,pharmacology Serpins/biosynthesis,pharmacology Time Factors Transfection Tumor Cells, Cultured
Chemicals
Antineoplastic Agents Proteins Recombinant Proteins SERPIN-B5 Serine Proteinase Inhibitors Serpins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sheng S
Division of Cancer Genetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Carey J
Seftor E A
Dias L
Hendrix M J
Sager R
References (55)
55 references, click to expand
  1. Tumor cell interactions with the extracellular matrix during invasion and metastasis.
    Annu Rev Cell Biol. 1993;9:541-73 PMID: 8280471
  2. Inhibition of invasion of HT1080 sarcoma cells expressing recombinant plasminogen activator inhibitor 2.
    Cancer Res. 1993 Dec 15;53(24):6051-7 PMID: 8261421
  3. Requirement for receptor-bound urokinase in plasmin-dependent cellular conversion of latent TGF-beta to TGF-beta.
    J Cell Physiol. 1994 Mar;158(3):398-407 PMID: 8126064
  4. Urokinase-type plasminogen activator and its receptor: new targets for anti-metastatic therapy?
    Trends Pharmacol Sci. 1994 Jan;15(1):25-9 PMID: 8140655
  5. Contrasting roles for integrin beta 1 and beta 5 cytoplasmic domains in subcellular localization, cell proliferation, and cell migration.
    J Cell Biol. 1994 Apr;125(2):447-60 PMID: 7512969
  6. Actin-dependent motile forces and cell motility.
    Curr Opin Cell Biol. 1994 Feb;6(1):82-6 PMID: 8167030
  7. Induction of cell migration by pro-urokinase binding to its receptor: possible mechanism for signal transduction in human epithelial cells.
    J Cell Biol. 1994 Jul;126(1):259-70 PMID: 7517943
  8. Biological implications of a 3 A structure of dimeric antithrombin.
    Structure. 1994 Apr 15;2(4):257-70 PMID: 8087553
  9. Function of maspin.
    Science. 1994 Sep 23;265(5180):1893-4 PMID: 8091216
  10. Production, purification, and characterization of recombinant maspin proteins.
    J Biol Chem. 1994 Dec 9;269(49):30988-93 PMID: 7983035
  11. Overexpression of plasminogen activator inhibitor 2 in human melanoma cells inhibits spontaneous metastasis in scid/scid mice.
    Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):205-9 PMID: 7816818
  12. Plasminogen activator inhibitor-2: prognostic relevance in 1012 patients with primary breast cancer.
    Cancer Res. 1995 Apr 1;55(7):1423-7 PMID: 7882345
  13. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia.
    Cell. 1995 Apr 7;81(1):53-62 PMID: 7536630
  14. What do dysfunctional serpins tell us about molecular mobility and disease?
    Nat Struct Biol. 1995 Feb;2(2):96-113 PMID: 7749926
  15. The tumor suppressor maspin does not undergo the stressed to relaxed transition or inhibit trypsin-like serine proteases. Evidence that maspin is not a protease inhibitory serpin.
    J Biol Chem. 1995 Jun 30;270(26):15832-7 PMID: 7797587
  16. Crystal structure of an uncleaved serpin reveals the conformation of an inhibitory reactive loop.
    Nat Struct Biol. 1994 Apr;1(4):251-8 PMID: 7656054
  17. Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor-1.
    Nat Struct Biol. 1995 Oct;2(10):891-7 PMID: 7552714
  18. RNA genetics of breast cancer: maspin as paradigm.
    Cold Spring Harb Symp Quant Biol. 1994;59:537-46 PMID: 7587110
  19. alpha-2 Macroglobulin receptor/Ldl receptor-related protein(Lrp)-dependent internalization of the urokinase receptor.
    J Cell Biol. 1995 Dec;131(6 Pt 1):1609-22 PMID: 8522616
  20. Stimulation of membrane ruffling and MAP kinase activation by distinct effectors of RAS.
    Science. 1996 Feb 9;271(5250):810-2 PMID: 8628998
  21. Ovalbumin: a secreted protein without a transient hydrophobic leader sequence.
    Proc Natl Acad Sci U S A. 1978 Jan;75(1):94-8 PMID: 272676
  22. Chicken ovalbumin contains an internal signal sequence.
    Nature. 1979 Sep 13;281(5727):117-21 PMID: 471058
  23. The signal sequence of ovalbumin is located near the NH2 terminus.
    J Biol Chem. 1982 Oct 25;257(20):12245-51 PMID: 6749856
  24. Tumor cell autocrine motility factor.
    Proc Natl Acad Sci U S A. 1986 May;83(10):3302-6 PMID: 3085086
  25. The opposing effects of basic fibroblast growth factor and transforming growth factor beta on the regulation of plasminogen activator activity in capillary endothelial cells.
    J Cell Biol. 1987 Aug;105(2):957-63 PMID: 3114269
  26. Distinctive traits of normal and tumor-derived human mammary epithelial cells expressed in a medium that supports long-term growth of both cell types.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1249-53 PMID: 2919173
  27. Interaction of plasminogen activator inhibitor (PAI-1) with vitronectin.
    J Biol Chem. 1989 Apr 15;264(11):6339-43 PMID: 2467912
  28. Asparagine residue in the rho gene product is the modification site for botulinum ADP-ribosyltransferase.
    J Biol Chem. 1989 May 25;264(15):8602-5 PMID: 2498316
  29. Effect of scatter factor on motility of epithelial cells and fibroblasts.
    J Cell Physiol. 1989 Jun;139(3):565-9 PMID: 2525565
  30. Tumor suppressor genes: the puzzle and the promise.
    Science. 1989 Dec 15;246(4936):1406-12 PMID: 2574499
  31. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis.
    EMBO J. 1990 Feb;9(2):467-74 PMID: 1689240
  32. The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants.
    J Biol Chem. 1990 Apr 15;265(11):6453-60 PMID: 2156852
  33. Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors.
    J Biol Chem. 1990 Jun 15;265(17):9904-8 PMID: 2161846
  34. Microinjection of recombinant p21rho induces rapid changes in cell morphology.
    J Cell Biol. 1990 Sep;111(3):1001-7 PMID: 2118140
  35. Purified scatter factor stimulates epithelial and vascular endothelial cell migration.
    Proc Soc Exp Biol Med. 1990 Oct;195(1):34-43 PMID: 2144630
  36. Plasminogen-activator inhibitor type 1 is a potent natural inhibitor of extracellular matrix degradation by fibrosarcoma and colon carcinoma cells.
    Proc Natl Acad Sci U S A. 1990 Sep;87(18):6939-43 PMID: 2169614
  37. Tumor progression in four mammary epithelial cell lines derived from the same patient.
    Cancer Res. 1990 Nov 15;50(22):7351-7 PMID: 1977518
  38. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein.
    J Biol Chem. 1992 Feb 5;267(4):2524-9 PMID: 1733949
  39. Urokinase-type plasminogen activator mediates basic fibroblast growth factor-induced bovine endothelial cell migration independent of its proteolytic activity.
    J Cell Physiol. 1992 Feb;150(2):258-63 PMID: 1734031
  40. Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines.
    J Cell Physiol. 1992 Mar;150(3):534-44 PMID: 1537883
  41. Cell adhesion molecule uvomorulin expression in human breast cancer cell lines: relationship to morphology and invasive capacities.
    Cell Growth Differ. 1991 Aug;2(8):365-72 PMID: 1793731
  42. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors.
    Cell. 1992 Aug 7;70(3):389-99 PMID: 1643657
  43. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
    Cell. 1992 Aug 7;70(3):401-10 PMID: 1643658
  44. Suppression of melanoma cell motility factor receptor expression by retinoic acid.
    Cancer Res. 1992 Sep 15;52(18):4878-84 PMID: 1325286
  45. Interleukin 6 promotes epithelial migration by a fibronectin-dependent mechanism.
    J Cell Physiol. 1992 Oct;153(1):1-5 PMID: 1522123
  46. Prognostic value of urokinase-type plasminogen activator in 671 primary breast cancer patients.
    Cancer Res. 1992 Nov 1;52(21):6101-5 PMID: 1394237
  47. Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor.
    EMBO J. 1992 Dec;11(13):4825-33 PMID: 1334458
  48. Cell motility, invasion, and malignancy induced by overexpression of K-FGF or bFGF.
    Exp Cell Res. 1993 Feb;204(2):295-301 PMID: 8440326
  49. Expression of complete keratin filaments in mouse L cells augments cell migration and invasion.
    Proc Natl Acad Sci U S A. 1993 May 1;90(9):4261-5 PMID: 7683431
  50. A re-examination of the molecular basis of cell movement.
    Immunol Cell Biol. 1993 Apr;71 ( Pt 2):131-9 PMID: 8486396
  51. High levels of urokinase-type plasminogen activator and its inhibitor PAI-1 in cytosolic extracts of breast carcinomas are associated with poor prognosis.
    Cancer Res. 1993 Jun 1;53(11):2513-21 PMID: 8388317
  52. Type-2 plasminogen-activator inhibitor is a substrate for trophoblast transglutaminase and factor XIIIa. Transglutaminase-catalyzed cross-linking to cellular and extracellular structures.
    Eur J Biochem. 1993 May 15;214(1):141-6 PMID: 8099547
  53. Overexpression of urokinase receptor increases matrix invasion without altering cell migration in a human osteosarcoma cell line.
    Cancer Res. 1993 Jul 1;53(13):3109-17 PMID: 8391387
  54. The role of conformational change in serpin structure and function.
    Bioessays. 1993 Jul;15(7):461-7 PMID: 8379949
  55. Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells.
    Science. 1994 Jan 28;263(5146):526-9 PMID: 8290962
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.21.11669
Published
1996-10-15
Pages
11669-74
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38116
Subset
IM
Grants
NCI NIH HHS · CA59702 · United States
NCI NIH HHS · CA61253 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.21.11669 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2