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. 1992 Jun 1;117(5):1101–1107. doi: 10.1083/jcb.117.5.1101

Requirement of the integrin beta 3 subunit for carcinoma cell spreading or migration on vitronectin and fibrinogen

PMCID: PMC2289489  PMID: 1374415

Abstract

FG human pancreatic carcinoma cells use integrin alpha v beta 5 as their primary vitronectin receptor since they fail to express integrin alpha v beta 3. These cells are unable to form focal contacts, spread, or migrate on vitronectin but readily do so on collagen in a beta 1 integrin-dependent manner. Transfection of FG cells with a cDNA encoding the integrin beta 3 subunit results in the surface expression of a functional integrin alpha v beta 3 heterodimer providing these cells with novel adhesive and biological properties. Specifically, FG cells expressing beta 3 acquire the capacity to attach and spread on vitronectin as well as fibrinogen with beta 3 localization to focal contacts. Moreover, these cells gain the capacity to migrate through a porous membrane in response to either vitronectin or fibrinogen. These results demonstrate that the beta 3 and beta 5 integrin subunits when associated with alpha v, promote distinct cellular responses to a vitronectin extracellular environment.

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Selected References

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  1. Adams J. C., Watt F. M. Expression of beta 1, beta 3, beta 4, and beta 5 integrins by human epidermal keratinocytes and non-differentiating keratinocytes. J Cell Biol. 1991 Nov;115(3):829–841. doi: 10.1083/jcb.115.3.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albelda S. M., Mette S. A., Elder D. E., Stewart R., Damjanovich L., Herlyn M., Buck C. A. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res. 1990 Oct 15;50(20):6757–6764. [PubMed] [Google Scholar]
  3. Bates R. C., Rankin L. M., Lucas C. M., Scott J. L., Krissansen G. W., Burns G. F. Individual embryonic fibroblasts express multiple beta chains in association with the alpha v integrin subunit. Loss of beta 3 expression with cell confluence. J Biol Chem. 1991 Oct 5;266(28):18593–18599. [PubMed] [Google Scholar]
  4. Bodary S. C., McLean J. W. The integrin beta 1 subunit associates with the vitronectin receptor alpha v subunit to form a novel vitronectin receptor in a human embryonic kidney cell line. J Biol Chem. 1990 Apr 15;265(11):5938–5941. [PubMed] [Google Scholar]
  5. Buck C. A., Horwitz A. F. Integrin, a transmembrane glycoprotein complex mediating cell-substratum adhesion. J Cell Sci Suppl. 1987;8:231–250. doi: 10.1242/jcs.1987.supplement_8.13. [DOI] [PubMed] [Google Scholar]
  6. Burridge K., Fath K., Kelly T., Nuckolls G., Turner C. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu Rev Cell Biol. 1988;4:487–525. doi: 10.1146/annurev.cb.04.110188.002415. [DOI] [PubMed] [Google Scholar]
  7. Busk M., Pytela R., Sheppard D. Characterization of the integrin alpha v beta 6 as a fibronectin-binding protein. J Biol Chem. 1992 Mar 25;267(9):5790–5796. [PubMed] [Google Scholar]
  8. Carter W. G., Wayner E. A., Bouchard T. S., Kaur P. The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells. J Cell Biol. 1990 Apr;110(4):1387–1404. doi: 10.1083/jcb.110.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Charo I. F., Bekeart L. S., Phillips D. R. Platelet glycoprotein IIb-IIIa-like proteins mediate endothelial cell attachment to adhesive proteins and the extracellular matrix. J Biol Chem. 1987 Jul 25;262(21):9935–9938. [PubMed] [Google Scholar]
  10. Cheresh D. A., Berliner S. A., Vicente V., Ruggeri Z. M. Recognition of distinct adhesive sites on fibrinogen by related integrins on platelets and endothelial cells. Cell. 1989 Sep 8;58(5):945–953. doi: 10.1016/0092-8674(89)90946-x. [DOI] [PubMed] [Google Scholar]
  11. Cheresh D. A., Harper J. R. Arg-Gly-Asp recognition by a cell adhesion receptor requires its 130-kDa alpha subunit. J Biol Chem. 1987 Feb 5;262(4):1434–1437. [PubMed] [Google Scholar]
  12. Cheresh D. A. Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6471–6475. doi: 10.1073/pnas.84.18.6471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cheresh D. A., Smith J. W., Cooper H. M., Quaranta V. A novel vitronectin receptor integrin (alpha v beta x) is responsible for distinct adhesive properties of carcinoma cells. Cell. 1989 Apr 7;57(1):59–69. doi: 10.1016/0092-8674(89)90172-4. [DOI] [PubMed] [Google Scholar]
  14. Cheresh D. A., Spiro R. C. Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. J Biol Chem. 1987 Dec 25;262(36):17703–17711. [PubMed] [Google Scholar]
  15. Dejana E., Colella S., Conforti G., Abbadini M., Gaboli M., Marchisio P. C. Fibronectin and vitronectin regulate the organization of their respective Arg-Gly-Asp adhesion receptors in cultured human endothelial cells. J Cell Biol. 1988 Sep;107(3):1215–1223. doi: 10.1083/jcb.107.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Felding-Habermann B., Ruggeri Z. M., Cheresh D. A. Distinct biological consequences of integrin alpha v beta 3-mediated melanoma cell adhesion to fibrinogen and its plasmic fragments. J Biol Chem. 1992 Mar 15;267(8):5070–5077. [PubMed] [Google Scholar]
  17. Freed E., Gailit J., van der Geer P., Ruoslahti E., Hunter T. A novel integrin beta subunit is associated with the vitronectin receptor alpha subunit (alpha v) in a human osteosarcoma cell line and is a substrate for protein kinase C. EMBO J. 1989 Oct;8(10):2955–2965. doi: 10.1002/j.1460-2075.1989.tb08445.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Horwitz A., Duggan K., Buck C., Beckerle M. C., Burridge K. Interaction of plasma membrane fibronectin receptor with talin--a transmembrane linkage. Nature. 1986 Apr 10;320(6062):531–533. doi: 10.1038/320531a0. [DOI] [PubMed] [Google Scholar]
  19. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  20. Kramer R. H., Cheng Y. F., Clyman R. Human microvascular endothelial cells use beta 1 and beta 3 integrin receptor complexes to attach to laminin. J Cell Biol. 1990 Sep;111(3):1233–1243. doi: 10.1083/jcb.111.3.1233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  22. McLean J. W., Vestal D. J., Cheresh D. A., Bodary S. C. cDNA sequence of the human integrin beta 5 subunit. J Biol Chem. 1990 Oct 5;265(28):17126–17131. [PubMed] [Google Scholar]
  23. Moyle M., Napier M. A., McLean J. W. Cloning and expression of a divergent integrin subunit beta 8. J Biol Chem. 1991 Oct 15;266(29):19650–19658. [PubMed] [Google Scholar]
  24. Otey C. A., Burridge K. Patterning of the membrane cytoskeleton by the extracellular matrix. Semin Cell Biol. 1990 Oct;1(5):391–399. [PubMed] [Google Scholar]
  25. Otey C. A., Pavalko F. M., Burridge K. An interaction between alpha-actinin and the beta 1 integrin subunit in vitro. J Cell Biol. 1990 Aug;111(2):721–729. doi: 10.1083/jcb.111.2.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ramaswamy H., Hemler M. E. Cloning, primary structure and properties of a novel human integrin beta subunit. EMBO J. 1990 May;9(5):1561–1568. doi: 10.1002/j.1460-2075.1990.tb08275.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ruoslahti E., Pierschbacher M. D. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. doi: 10.1126/science.2821619. [DOI] [PubMed] [Google Scholar]
  28. Sheppard D., Rozzo C., Starr L., Quaranta V., Erle D. J., Pytela R. Complete amino acid sequence of a novel integrin beta subunit (beta 6) identified in epithelial cells using the polymerase chain reaction. J Biol Chem. 1990 Jul 15;265(20):11502–11507. [PubMed] [Google Scholar]
  29. Straus A. H., Carter W. G., Wayner E. A., Hakomori S. Mechanism of fibronectin-mediated cell migration: dependence or independence of cell migration susceptibility on RGDS-directed receptor (integrin). Exp Cell Res. 1989 Jul;183(1):126–139. doi: 10.1016/0014-4827(89)90423-0. [DOI] [PubMed] [Google Scholar]
  30. Suzuki S., Huang Z. S., Tanihara H. Cloning of an integrin beta subunit exhibiting high homology with integrin beta 3 subunit. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5354–5358. doi: 10.1073/pnas.87.14.5354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tamkun J. W., DeSimone D. W., Fonda D., Patel R. S., Buck C., Horwitz A. F., Hynes R. O. Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell. 1986 Jul 18;46(2):271–282. doi: 10.1016/0092-8674(86)90744-0. [DOI] [PubMed] [Google Scholar]
  32. Vogel B. E., Tarone G., Giancotti F. G., Gailit J., Ruoslahti E. A novel fibronectin receptor with an unexpected subunit composition (alpha v beta 1). J Biol Chem. 1990 Apr 15;265(11):5934–5937. [PubMed] [Google Scholar]
  33. Wayner E. A., Orlando R. A., Cheresh D. A. Integrins alpha v beta 3 and alpha v beta 5 contribute to cell attachment to vitronectin but differentially distribute on the cell surface. J Cell Biol. 1991 May;113(4):919–929. doi: 10.1083/jcb.113.4.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yatohgo T., Izumi M., Kashiwagi H., Hayashi M. Novel purification of vitronectin from human plasma by heparin affinity chromatography. Cell Struct Funct. 1988 Aug;13(4):281–292. doi: 10.1247/csf.13.281. [DOI] [PubMed] [Google Scholar]

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