Skip to main content
Log in

Fibronectin in cell adhesion and invasion

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Summary

Fibronectin plays a major role in the adhesion of many cell types. The extent of cell adhesion in vitro is related not only to the ability of the cells to interact with matrix-bound fibronectin, when it is present, but also to the synthesis or lack of synthesis of fibronectin by the cells, and to the lack of deposition of synthesized fibronectin into an insoluble matrix surrounding the cells. Many malignant cells, regardless of whether they synthesize subnormal or normal amounts of fibronectin, fail to deposit that fibronectin into a surrounding insoluble matrix. The lack of fibronectin around such cells appears to reflect a general absence of extracellular matrix since other matrix components, such as collagen, laminin, and heparan sulfate proteoglycan, are concomitantly missing. Cells that lack their own cell surface fibronectin due either to lack of deposition or to lack of synthesis can nevertheless adhere to insoluble fibronectin matrices elaborated by other cells. These cellular characteristics appear to be associated with cell migration in vivo during embryogenesis, and the same characteristics may enhance the invasive potential of malignant cells. The remarkable effects that fibronectin has on cellular adhesion and the association of lack of extracellular matrix components with poorly differentiated and highly metastatic tumors in vivo mandates that more be learned about the molecular and cellular details of the interactions of cells with their surrounding matrix. Important information concerning tumor invasion will parallel such an understanding and may eventually become the basis for therapeutic approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cunningham LW, Fredericksen DW: Methods in enzymology, Vol 82 Part A, Structural and contractile proteins. Academic Press, New York, 1982, 913 pp.

    Google Scholar 

  2. Miller EJ: Chemistry of the collagens and their distribution. In: Piez KA, Reddi AH (eds) Connective tissue biochemistry. Elsevier-North Holland Press, Amsterdam (in press).

  3. Bornstein P, Sage H: Structurally distinct collagen types. Ann Rev Biochem (49): 957–1003, 1980.

    Google Scholar 

  4. Hascall VC, Hascall GT: Proteoglycans. In: Cell biology of extracellular matrix. Plenum Press, Hay ED (ed), New York, 1981, pp 39–63.

    Google Scholar 

  5. Ruoslahti E, Engvall E, Hayman EG: Fibronectin: Current concepts of its structure and functions. Col Res (1): 95–128, 1981.

    Google Scholar 

  6. Timpl R, Rohde H, Risteli L, Ott U, Robey PG, Martin GR: Laminin. Meth Enzymol (82): 831–838, 1982.

    Google Scholar 

  7. Grobstein C: Developmental role of intercellular matrix: retrospective and prospective. In: Slavkin HC, Greulich RC (eds) Extracellular matrix influences on gene expression. Academic Press, New York, 1975, pp 9–16.

    Google Scholar 

  8. Hayman EG, Ruoslahti E: Distribution of fetal bovine serum fibronectin and endogenous rat cell fibronectin in extracellular matrix. J Cell Biol (83): 255–259, 1979.

    Google Scholar 

  9. Oh E, Pierschbacher M, Ruoslahti E: Deposition of plasma fibronectin in tissues. Proc Natl Acad Sci USA (78): 3218–3221, 1981.

    Google Scholar 

  10. Mosher DF: Fibronectin. Prog Hemostas Thromb (5): 111–151, 1980.

    Google Scholar 

  11. Hynes RO, Yamada KM: Fibronectins: multifunctional modular glycoproteins. J Cell Biol (95): 369–377, 1982.

    Google Scholar 

  12. Keski-Oja J: Polymerization of a major surface-associated glycoprotein, fibronectin, in cultured fibroblasts. FEBS Letts (71): 325–329, 1976.

    Google Scholar 

  13. Wagner DD, Hynes RO: Topological arrangement of the major structural features of fibronectin. J Biol Chem (255): 4304–4312, 1980.

    Google Scholar 

  14. Klebe RJ: Isolation of a collagen-dependent cell attachment factor. Nature (250): 248–251, 1974.

    Google Scholar 

  15. Pearlstein E: Plasma membrane glycoprotein which mediates adhesion of fibroblasts to collagen. Nature (262): 497–500, 1976.

    Google Scholar 

  16. Grinnell F: Cell attachment and spreading factors. In: Guroff G (ed) Growth and maturation factors. John Wiley and Sons, Inc, 1983, pp 267–292.

  17. Grinnell F, Lang BR, Phan TV: Binding of plasma fibronectin to the surfaces of BHK cells in suspension at 4°C. Exp Cell Res (142): 499–504, 1982.

    Google Scholar 

  18. Pierschbacher MD, Ruoslahti E, Sundelin J, Lind P, Peterson PA: The cell attachment domain of fibronectin. J Biol Chem (257): 9593–9597, 1982.

    Google Scholar 

  19. Pierschbacher MD, Hayman EG, Ruoslahti E: Synthetic peptide with cell attachment activity of fibronectin. Proc Natl Acad Sci USA (80): 1224–1227, 1983.

    Google Scholar 

  20. Vaheri A, Ruoslahti E: Disappearance of a major cell-type specific surface glycoprotein antigen (SF) after transformation of fibroblasts by rous sarcoma virus. Int J Cancer (13): 579–586, 1974.

    Google Scholar 

  21. Gahmberg CG, Kiehn D, Hakomori S: Changes in a surface-labelled galactoprotein and in glycolipid concentrations in cells transformed by a temperature-sensitive polyoma virus mutant. Nature (248): 413–415, 1974.

    Google Scholar 

  22. Furcht LT, Mosher DF, Wendelschafer-Crabb G, Woodbridge PA, Foidart J-M. Dexamethasone-induced accumulation of a fibronectin and collagen extracellular matrix in transformed human cells. Nature (277): 393–395, 1979.

    Google Scholar 

  23. Nielson SE, Puck TT: Deposition of fibronectin in the course of reverse transformation of Chinese hamster ovary cells by cyclic AMP. Proc Natl Acad Sci USA (77): 985–989, 1980.

    Google Scholar 

  24. Hayman EG, Engvall E, Ruoslahti E: Butyrate restores fibronectin at cell surface of transformed cells. Exp Cell Res (127): 478–481, 1980.

    Google Scholar 

  25. Hayman EG, Oldberg Å, Martin GR, Ruoslahti E: Codistribution of heparan sulfate proteoglycan, laminin, and fibronectin in the extracellular matrix of normal rat kidney cells and their coordinate absence in transformed cells. J Cell Biol (94): 28–35, 1982.

    Google Scholar 

  26. Hedman K, Johansson S, Vartio T, Kjéllen L, Vaheri A, Höök M: Structure of the pericellular matrix: Association of heparan and chondroitin sulfates with fibronectin-procollagen fibers. Cell (28): 663–671, 1982.

    Google Scholar 

  27. Alitalo K, Keski-Oja J, Hedman K, Vaheri A: Loss of different pericellular matrix components of rat cells transformed with a T-class ts mutant of Rous sarcoma virus. Virology (119): 347–357, 1982.

    Google Scholar 

  28. Bornstein P, Ash JF: Cell surface-associated structural proteins in connective tissue cells. Proc Natl Acad Sci USA (74): 2480–2484, 1977.

    Google Scholar 

  29. Vaheri A, Kurkinen M, Lehto V-P, Linder E, Timpl R: Codistribution of pericellular matrix proteins in cultured fibroblasts and loss in transformation: Fibronectin and procollagen. Proc Natl Acad Sci USA (75): 4944–4948, 1978.

    Google Scholar 

  30. Furcht LT, Mosher DF, Wendelschafer-Crabb G: Immunocytochemical localization of fibronectin (LETS protein) on the surface of L6 myoblasts: light and electron microscopic studies. Cell (13): 263–271, 1978.

    Google Scholar 

  31. Asch BB, Kamat BR, Burstein NA: Interactions of normal, dysplastic, and malignant mammary epithelial cells with fibronectin in vivo and in vitro. Cancer Res (41): 2115–2125, 1981.

    Google Scholar 

  32. Labat-Robert J, Birembaut P, Robert L, Adnet JJ: Modification of fibronectin distribution pattern in solid human tumors. Diag Histopath (4): 299–306, 1981.

    Google Scholar 

  33. Albrechtsen R, Nielsen M, Wewer U, Engvall E, Ruoslahti E: Basement membrane changes in breast cancer detected by immunohistochemical staining for laminin. Cancer Res (41): 5076–5081, 1981.

    Google Scholar 

  34. Siegal GP, Barsky SH, Terranova VP, Liotta LA: Stages of neoplastic transformation of human breast tissue as monitored by dissolution of basement membrane components. Invasion Metas (1): 54–70, 1981.

    Google Scholar 

  35. Burtin P, Chavanel G, Foidart JM, Andre J: Alterations of the basement membrane and connective tissue antigens in human metastatic lymph nodes. Int J Cancer (31): 719–726, 1982.

    Google Scholar 

  36. Kramer RH, Nicolson GL: Interactions of tumor cells with vascular endothelial cell monolayers: a model for metastatic invasion. Proc Natl Acad Sci USA (76): 5704–5708, 1979.

    Google Scholar 

  37. Jones PA, DeClerck YA: Destruction of extracellular matrices containing glycoproteins, elastin, and collagen by metastatic human tumor cells. Cancer Res (40): 3222–3227, 1980.

    Google Scholar 

  38. Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S: Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature (284): 67–68, 1980.

    Google Scholar 

  39. Nicolson GL: Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. J Histochem Cytochem (30): 214–220, 1982.

    Google Scholar 

  40. Der CJ, Standbridge EJ: Lack of correlation between the decreased expression of cell surface LETS protein and tumorigenicity in human cell hybrids. Cell (15): 1241–1251, 1978.

    Google Scholar 

  41. Kahn P, Shin SI: Cellular tumorigenicity in nude mice: Test of associations among loss of cell-surface fibronectin, anchorage independence, and tumor-forming ability. J Cell Biol (82): 1–16, 1979.

    Google Scholar 

  42. Neri A, Ruoslahti E, Nicolson GL: Distribution of fibronectin on clonal cell lines of a rat mammary adenocarcinoma growing in vitro and in vivo at primary and metastatic sites. Cancer Res (41): 5082–5095, 1981.

    Google Scholar 

  43. Keski-Oja J, Gahmberg CG, Alitalo K: Pericellular matrix and cell surface glycoproteins of virus-transformed mouse epithelial cells. Cancer Res (42): 1147–1153, 1982.

    Google Scholar 

  44. Schwartz CE, Ruoslahti E: Concurrent modulation of cell surface fibronectin and adhesion to fibronectin in hepatoma cells. Exp Cell Res (143): 457–461, 1983.

    Google Scholar 

  45. Sell S, Ruoslahti E: Expression of fibronectin and laminin in the rat liver after partial hepatectomy, during carcinogenesis, and in transplantable hepatocellular carcinomas. JNCI (69): 1105–1114, 1982.

    Google Scholar 

  46. Stenman S, Vaheri A: Fibronectin in human solid tumors. Int J Cancer (27): 427–435, 1981.

    Google Scholar 

  47. Smith HS, Riggs JL, Mosesson MW: Production of fibronectin by human epithelial cells in culture. Cancer Res (39): 4138–4144, 1979.

    Google Scholar 

  48. Hayman EG, Engvall E, Ruoslahti E: Concomitant loss of cell surface fibronectin and laminin from transformed rat kidney cells. J Cell Biol (88): 352–357, 1981.

    Google Scholar 

  49. Wagner DD, Raymond I, Destree AT, Hynes RO: Similarities and differences between the fibronectins of normal and transformed hamster cells. J Biol Chem (256): 11708–11715, 1981.

    Google Scholar 

  50. Oldberg Å, Linney E, Ruoslahti E: Molecular cloning and nucleotide sequence of a cDNA clone coding for the cell attachment domain in human fibronectin. J Biol Chem (258): 10193–10196, 1983.

    Google Scholar 

  51. Ali IU, Hunter T: Structural comparison of fibronectins from normal and transformed cells. J Biol Chem (256): 7671–7677, 1981.

    Google Scholar 

  52. Yamada KM, Yamada S, Pastan I: Cell surface protein partially restores morphology, adhesiveness, and contact inhibition of movement to transformed fibroblasts. Proc Natl Acad Sci USA: 1217–1221, 1976.

  53. Ali IU, Mautner V, Lanza R, Hynes RO: Restoration of normal morphology, adhesion and cytoskeleton in transformed cells by addition of a transformation-sensitive surface protein. Cell (11): 115–126, 1977.

    Google Scholar 

  54. Nicolson GL, Irimura T, Gonzalez R, Ruoslahti E: The role of fibronectin in adhesion of metastatic melanoma cells to endothelial cells and their basal lamina. Exp Cell Res (135): 461–465, 1981.

    Google Scholar 

  55. Edwards JG, Dysart J McK, Hughes RC: Cellular adhesiveness reduced in ricin-resistant hamster fibroblasts. Nature (264): 66–68, 1976.

    Google Scholar 

  56. Erickson CA, Tosney KW, Weston JA: Analysis of migratory behavior of neural crest and fibroblastic cells in embryonic tissues. Dev Biol (77): 142–156, 1980.

    Google Scholar 

  57. Bronner-Fraser M: Distribution of latex beads and retinal pigment epithelial cells along the ventral neural crest pathway. Dev Biol (91): 50–63, 1982.

    Google Scholar 

  58. Kramer RH, Gonzalez R, Nicolson GL: Metastatic tumor cells adhere preferentially to the extracellular matrix under-lying vascular endothelial cells. Int J Cancer (26): 639–645, 1980.

    Google Scholar 

  59. Vlodavsky I, Ariav Y, Atzmon R, Fuks Z: Tumor cell attachment to the vascular endothelium and subsequent degradation of the subendothelial matrix. Exp Cell Res (140): 149–159, 1982.

    Google Scholar 

  60. Ali IU, Hynes RO: Effects of LETS glycoprotein on cell motility. Cell (14): 439–446, 1978.

    Google Scholar 

  61. Schor SL, Schor AM, Bazill GW: The effects of fibronectin on the migration of human foreskin fibroblasts and Syrian hamster melanoma cells into three-dimensional gels of native collagen fibres. J Cell Sci (48): 301–304, 1981.

    Google Scholar 

  62. Brennan MJ, Oldberg Å, Hayman EG, Ruoslahti E: Effect of a proteoglycan produced by rat tumor cells on their adhesion to fibronectin-collagen substrata. Cancer Res (43): 4302–4307, 1983.

    Google Scholar 

  63. Iozzo RV, Wight TM: Isolation and characterization of proteoglycans synthesized by human colon and colon carcinoma. J Biol Chem (257): 11135–11144, 1982.

    Google Scholar 

  64. Oldberg Å, Hauman EG, Ruoslahti E: Isolation of a chondroitin sulfate proteoglycan from a rat yolk sac tumor and immunochemical demonstration of its cell surface localization. J Biol Chem (256) 10847–10852, 1981.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by grant CA 28896 and Cancer Center Support Grant CA 30199 from the National Cancer Institute, Department of Health and Human Services.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruoslahti, E. Fibronectin in cell adhesion and invasion. Cancer Metast Rev 3, 43–51 (1984). https://doi.org/10.1007/BF00047692

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00047692

Keywords

Navigation