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Studying actin-dependent processes in tissue culture

Nature Reviews Molecular Cell Biology volume 3, pages 137–141 (2002)Cite this article

Abstract

The cytoskeletal organization of cells that are grown in tissue culture is often very different from that of cells in living organisms. This casts some doubt as to whether information that comes from studying actin-dependent cellular processes — such as cell motility or differentiation — in cells that are cultured under these conditions is physiologically relevant. Studies on cells grown in improved two-dimensional- and three-dimensional-culture systems that closely mimic the in vivo extracellular-matrix environment should provide a more accurate picture of actin-cytoskeletal function in the living organism.

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Figure 1: Diagram of fibroblasts growing on two-dimensional or three-dimensional substrates.
Figure 2: Morphology of fibroblasts migrating inside a collagen gel.
Figure 3: Epithelial cells sit on ECM but fibroblasts invade.
Figure 4: Diagrammatic summary of experiments on epithelial–ECM interaction.
Figure 5: Diagram showing the effect of matrix molecules on the basal surface of corneal epithelium.
Figure 6: Diagram showing lactation and involution cycle of the mammary gland.

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References

  1. Voytik-Harbin, S. L. Three-dimensional extracellular matrix substrates for cell culture. Methods Cell Biol. 63, 561–581 (2001).

    Article  CAS  Google Scholar 

  2. Stoker, A. W., Streuli, C. H., Martins-Green, M. & Bissell, M. J. Designer microenvironments for the analysis of cell and tissue function. Curr. Opin. Cell Biol. 2, 864–874 (1990).

    Article  CAS  Google Scholar 

  3. Vasioukhin, V. & Fuchs, E. Actin dynamics and cell–cell adhesion in epithelia. Curr. Opin. Cell Biol. 13, 76–84 (2001).

    Article  CAS  Google Scholar 

  4. Hay, E. D. (ed.) Cell Biology of Extracellular Matrix (Plenum Press, New York, 1991).

    Book  Google Scholar 

  5. Giancotti, F. G. & Ruoslahti, E. Integrin signaling. Science 285, 1028–1032 (1999).

    Article  CAS  Google Scholar 

  6. Ehrmann, R. L. & Gey, G. O. The growth of cells on a transplant gel of reconstituted rat-tail collagen. J. Natl Cancer Inst. 16, 1375–1402 (1956).

    CAS  Google Scholar 

  7. Konigsberg, I. R. & Hauschka, S. D. Cell and Tissue Interactions in the Reproductions of Cell Type (ed. Locke, M.) (Academic Press, New York, 1965).

    Book  Google Scholar 

  8. Kleinman, H. K., Klebe, R. J. & Martin, G. R. Role of collagenous matrices in the adhesion and growth of cells. J. Cell Biol. 88, 473–485 (1981).

    Article  CAS  Google Scholar 

  9. Hay, E. D. & Dodson, J. W. Secretion of collagen by corneal epithelium. I. Morphology of the collagenous products produced by isolated epithelia grown on frozen- killed lens. J. Cell Biol. 57, 190–213 (1973).

    Article  CAS  Google Scholar 

  10. Herman, I. M., Crisona, N. J. & Pollard, T. D. Relation between cell activity and the distribution of cytoplasmic actin and myosin. J. Cell Biol. 90, 84–91 (1981).

    Article  CAS  Google Scholar 

  11. Tomasek, J. J., Hay, E. D. & Fujiwara, K. Collagen modulates cell shape and cytoskeleton of embryonic corneal and fibroma fibroblasts: distribution of actin, α-actinin, and myosin. Dev. Biol. 92, 107–122 (1982).

    Article  CAS  Google Scholar 

  12. Kano, Y., Katoh, K., Masuda, M. & Fujiwara, K. Macromolecular composition of stress fiber-plasma membrane attachment sites in endothelial cells in situ. Circ. Res. 79, 1000–1006 (1996).

    Article  CAS  Google Scholar 

  13. Elsdale, T. & Bard, J. Collagen substrata for studies on cell behavior. J. Cell Biol. 54, 626–637 (1972).

    Article  CAS  Google Scholar 

  14. Bard, J. B. & Hay, E. D. The behavior of fibroblasts from the developing avian cornea. Morphology and movement in situ and in vitro. J. Cell Biol. 67, 400–418 (1975).

    Article  CAS  Google Scholar 

  15. Overton, J. Response of epithelial and mesenchymal cells to culture on basement lamella observed by scanning microscopy. Exp. Cell Res. 105, 313–323 (1977).

    Article  CAS  Google Scholar 

  16. Meier, S. & Hay, E. D. Control of corneal differentiation by extracellular materials. Collagen as a promoter and stabilizer of epithelial stroma production. Dev. Biol. 38, 249–270 (1974).

    Article  CAS  Google Scholar 

  17. Svoboda, K. K. & Hay, E. D. Embryonic corneal epithelial interaction with exogenous laminin and basal lamina is F-actin dependent. Dev. Biol. 123, 455–469 (1987).

    Article  CAS  Google Scholar 

  18. Sugrue, S. P. & Hay, E. D. Response of basal epithelial cell surface and cytoskeleton to solubilized extracellular matrix molecules. J. Cell Biol. 91, 45–54 (1981).

    Article  CAS  Google Scholar 

  19. Sugrue, S. P. & Hay, E. D. The identification of extracellular matrix (ECM) binding sites on the basal surface of embryonic corneal epithelium and the effect of ECM binding on epithelial collagen production. J. Cell Biol. 102, 1907–1916 (1986).

    Article  CAS  Google Scholar 

  20. Chu, C. L., Reenstra, W. R., Orlow, D. L. & Svoboda, K. K. Erk and PI-3 kinase are necessary for collagen binding and actin reorganization in corneal epithelia. Invest. Ophthalmol. Vis. Sci. 41, 3374–3382 (2000).

    CAS  Google Scholar 

  21. Singer, R. H. The cytoskeleton and mRNA localization. Curr. Opin. Cell Biol. 4, 15–19 (1992).

    Article  CAS  Google Scholar 

  22. Oleynikov, Y. & Singer, R. H. RNA localization: different zipcodes, same postman? Trends Cell Biol. 8, 381–383 (1998).

    Article  CAS  Google Scholar 

  23. Talhouk, R. S., Werb, Z. & Bissell, M. J. in Epithelial Organization and Development (ed. Fleming, T. P.) 329–385 (Chapman and Hall, New York, 1992).

    Book  Google Scholar 

  24. Bissell, M. J. et al. Tissue structure, nuclear organization, and gene expression in normal and malignant breast. Cancer Res. 59, S1757–S1763; discussion S1763–S1764 (1999).

    Google Scholar 

  25. Emerman, J. T., Enami, J., Pitelka, D. R. & Nandi, S. Hormonal effects on intracellular and secreted casein in cultures of mouse mammary epithelial cells on floating collagen membranes. Proc. Natl Acad. Sci. USA 74, 4466–4470 (1977).

    Article  CAS  Google Scholar 

  26. Streuli, C. H. & Bissell, M. J. Expression of extracellular matrix components is regulated by substratum. J. Cell Biol. 110, 1405–1415 (1990).

    Article  CAS  Google Scholar 

  27. Aggeler, J. et al. Cytodifferentiation of mouse mammary epithelial cells cultured on a reconstituted basement membrane reveals striking similarities to development in vivo. J. Cell Sci. 99, 407–417 (1991).

    Google Scholar 

  28. Streuli, C. H., Bailey, N. & Bissell, M. J. Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell–cell interaction and morphological polarity. J. Cell Biol. 115, 1383–1395 (1991).

    Article  CAS  Google Scholar 

  29. Damsky, C. H. & Werb, Z. Signal transduction by integrin receptors for extracellular matrix: cooperative processing of extracellular information. Curr. Opin. Cell Biol. 4, 772–781 (1992).

    Article  CAS  Google Scholar 

  30. Schmidhauser, C., Bissell, M. J., Myers, C. A. & Casperson, G. F. Extracellular matrix and hormones transcriptionally regulate bovine β-casein 5′ sequences in stably transfected mouse mammary cells. Proc. Natl Acad. Sci. USA 87, 9118–9122 (1990).

    Article  CAS  Google Scholar 

  31. Schmidhauser, C. et al. A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of β-casein gene expression. Mol. Biol. Cell 3, 699–709 (1992).

    Article  CAS  Google Scholar 

  32. Myers, C. A. et al. Characterization of BCE-1, a transcriptional enhancer regulated by prolactin and extracellular matrix and modulated by the state of histone acetylation. Mol. Cell. Biol. 18, 2184–2195. (1998).

    Article  CAS  Google Scholar 

  33. Muthuswamy, S. K., Li, D., Lelievre, S., Bissell, M. J. & Brugge, J. S. ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini. Nature Cell Biol. 3, 785–792 (2001).

    Article  CAS  Google Scholar 

  34. Harkin, D. G. & Hay, E. D. Effects of electroporation on the tubulin cytoskeleton and directed migration of corneal fibroblasts cultured within collagen matrices. Cell Motil. Cytoskeleton 35, 345–357 (1996).

    Article  CAS  Google Scholar 

  35. Voytik-Harbin, S. L., Rajwa, B. & Robinson, J. P. Three-dimensional imaging of extracellular matrix and extracellular matrix-cell interactions. Methods Cell Biol. 63, 583–597 (2001).

    Article  CAS  Google Scholar 

  36. Cukierman, E., Pankov, R., Stevens, D. R. & Yamada, K. M. Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712 (2001).

    Article  CAS  Google Scholar 

  37. Hay, E. D. & Svoboda, K. K. in Cell Shape: Determinants, Regulation and Regulatory Role (eds. Stein, W. D. & Bronner, F.) 147–172 (Academic Press, Orlando, 1989).

    Book  Google Scholar 

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Authors and Affiliations

  1. the Department of Cell Biology, Harvard Medical School, 220 Longwood Avenue, Goldenson, Boston, 342, Massachusetts, USA

    Deepika Walpita & Elizabeth Hay

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  1. Deepika Walpita
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  2. Elizabeth Hay
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Correspondence to Elizabeth Hay.

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DATABASES

Swiss-Prot

β1-integrin

β-casein

FAK

fibronectin

GFP

type IV collagen

 LocusLink

Rho

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Walpita, D., Hay, E. Studying actin-dependent processes in tissue culture. Nat Rev Mol Cell Biol 3, 137–141 (2002). https://doi.org/10.1038/nrm727

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