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Density-dependent regulation of cell growth: An example of a cell-cell recognition phenomenon

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Summary

Cell-to-cell contact can result in a variety of changes in the cell's physiology. For different cell types, this may include both the initiation as well as the cessation of cell growth and changes in the state of differentiation. This review examines in detail one such phenomenon, density-dependent inhibition of growth, which is observed with many fibroblasts in culture. Data are summarized which demonstrate that the cessation of growth at high cell density is in part a consequence of cell-to-cell contact. An approach to the study of the molecular basis of this phenomenon is presented based on the demonstration that plasma membranes, when bound to sparse growing cells, mimic contact inhibition of growth. The present status of attempts to purify plasma membrane proteins responsible for this effect are summarized, and the properties of these membrane proteins are compared to those of previously described “soluble” proteins that inhibit cellular growth.

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References

  1. Barbera, A.J. 1975.Dev. Biol. 46:167–191

    Article  PubMed  Google Scholar 

  2. Barbera, A.J., Marchese, R.B., Roth, S. 1973.Proc. Natl. Acad. Sci. USA 70:2–2486

    Google Scholar 

  3. Barondes, S.H. 1970.In: Neurosciences, Second Study Program. F.O. Schmitt, editor. pp. 747–760. Rockefeller University Press, New York

    Google Scholar 

  4. Barsh, G.S., Cunningham, D.D. 1977.J. Supramol. Struct. 7:61–77

    Article  PubMed  Google Scholar 

  5. Bellet, N.F., Vacquier, J.P., Vacquier, V.D. 1977.Biochem. Biophys. Res. Commun. 79:159–165

    Article  PubMed  Google Scholar 

  6. Brown, K.D., Holley, R.W. 1979.J. Cell. Physiol. 100:139–146

    Article  PubMed  Google Scholar 

  7. Brown, K.D., Yeh, Y.C., Holley, R.W. 1979.J. Cell. Physiol. 100:227–238

    Article  PubMed  Google Scholar 

  8. Bunge, R., Glaser, L., Lieberman, M.A., Raben, D., Salzer, J., Whittenberger, B., Woolsey, T.A. 1979.J. Supramol. Struct. 11:175–187

    Article  PubMed  Google Scholar 

  9. Burger, M.M., Jumblatt, J. 1977.In: Cell and Tissue Interaction J.W. Lash and M.M. Burger, editors. pp. 155–172. Plenum Press, New York

    Google Scholar 

  10. Caldwell, K.L., Munson, R., Jr., Glaser, L. 1981.J. Supramol. Struct. Suppl. 5:817

    Google Scholar 

  11. Carpenter, G., Cohen, S. 1979.Annu. Rev. Biochem. 48:193–216

    PubMed  Google Scholar 

  12. Cauldwell, C.B., Henkart, P., Humphreys, T. 1973.Biochemistry 12:3051–3055

    Article  PubMed  Google Scholar 

  13. Cohen, S., Carpenter, G., King, Jr., L. 1980.J. Biol. Chem. 255:4834–4842

    PubMed  Google Scholar 

  14. Das, M. 1980.Proc. Natl. Acad. Sci USA 77:112–116

    PubMed  Google Scholar 

  15. Datta, P., Natraj, C.V. 1980.Exp. Cell. Res. 125:431–439

    Article  PubMed  Google Scholar 

  16. Davies, P.F. 1980.J. Supramol. Struct. 13:211–218

    Article  PubMed  Google Scholar 

  17. Davies, P.F., Ross, R. 1980.Exp. Cell Res. 129:329–336

    Article  PubMed  Google Scholar 

  18. Dulbecco, R. 1970.Nature (London) 227:802–806

    Google Scholar 

  19. Dulbecco, R., Elkington, J. 1973.Nature (London) 246:197–199

    Google Scholar 

  20. Dulbecco, R., Stoker, M.G.P. 1970.Proc. Natl. Acad. Sci. USA 66:204–210

    PubMed  Google Scholar 

  21. Folkman, J., Moscona, A. 1978.Nature (London) 273:345–349

    Google Scholar 

  22. Fox, C.F., Vale, R., Peterson, S.W., Das, M. 1979.In: Hormones and Cell Culture. G. Sato and R. Ross, editors. pp. 143–158. Cold Spring Harbor Laboratory, New York

    Google Scholar 

  23. Frantz, C.N., Nathan, D.G., Scher, C.D. 1981.J. Cell. Biol. 88:51–56

    Article  PubMed  Google Scholar 

  24. Frazier, W., Glaser, L. 1979.Annu. Rev. Biochem. 48:491–523

    Article  PubMed  Google Scholar 

  25. Friedkin, M., Legg, A., Rozengurt, E. 1980.Exp. Cell Res. 129:23–30

    Article  PubMed  Google Scholar 

  26. Friedkin, M., Legg, A., Rozengurt, E. 1979.Proc. Natl. Acad. Sci. USA 76:3909–3912

    PubMed  Google Scholar 

  27. Glabe, C.G., Vacquier, V.D. 1977.Nature (London) 267:836–838

    Google Scholar 

  28. Glabe, C.G., Vacquier, V.D. 1978.Proc. Natl. Acad. Sci. USA 75:881–885

    PubMed  Google Scholar 

  29. Gospodarowicz, D., Delgado, D., Vladovsky, I. 1980.Proc. Natl. Acad. Sci. USA 77:4094–4098

    PubMed  Google Scholar 

  30. Gospodarowicz, D., Ill, C.R. 1980.Proc. Natl. Acad. Sci. USA 77:2726–2730

    PubMed  Google Scholar 

  31. Gottlieb, D.I., Glaser, L. 1980.Annu. Rev. Neurosci. 3:303–318

    Article  PubMed  Google Scholar 

  32. Gottlieb, D.I., Merrell, R., Glaser, L. 1974.Proc. Natl. Acad. Sci. USA 71:1800–1802

    PubMed  Google Scholar 

  33. Gottlieb, D.I., Rock, K., Glaser, L. 1976.Proc. Natl. Acad. Sci. USA 73:410–414

    PubMed  Google Scholar 

  34. Gysin, R., Moore, B.W., Proffitt, R.T., Deuel, T.F., Caldwell, K., Glaser, L. 1980.J. Biol. Chem. 255:1515–1520

    PubMed  Google Scholar 

  35. Harel, L., Jullien, M., Monti, M. de 1978.J. Cell. Physiol. 96:327–332

    Article  PubMed  Google Scholar 

  36. Heldin, C.-H., Westermark, B., Wasterson, Å. 1979.Nature (London) 282:419–420

    Google Scholar 

  37. Henkart, P., Humphreys, S., Humphreys, T. 1973.Biochemistry 12:3045–3050

    Article  PubMed  Google Scholar 

  38. Holley, R.W. 1975.Nature (London) 258:487–490

    Google Scholar 

  39. Holley, R.W., Armour, R., Baldwin, J.H. 1978.Proc. Natl. Acad. Sci. USA 75:339–341

    PubMed  Google Scholar 

  40. Holley, R.W., Armour, R., Baldwin, J.H., Brown, K.D., Yeh, Y.C. 1977.Proc. Natl. Acad. Sci. USA 74:5046–5050

    PubMed  Google Scholar 

  41. Holley, R.W. Kiernan J.A., 1968.Proc. Natl. Acad. Sci. USA 60:300–304

    PubMed  Google Scholar 

  42. Humphreys, S., Humphreys, T., Sano, J. 1977.J. Supramol. Struct. 7:339–351

    Article  PubMed  Google Scholar 

  43. Koch, K.S., Leffert, H.L. 1979.Cell 18:153–163

    PubMed  Google Scholar 

  44. Labourdette, G., Marks, L. 1975.Eur. J. Biochem. 58:73–79

    Article  PubMed  Google Scholar 

  45. Lieberman, M.A., Deuel, T.F., Glaser, L. 1981.FEBS Lett. (in press)

  46. Lieberman, M.A., Raben, D., Glaser, L. 1981.Exp. Cell Res. 126:45–48

    Google Scholar 

  47. Lieberman, M.A., Raben, D.M., Whittenberger, B., Glaser, L. 1979.J. Biol. Chem. 254:6357–6361

    PubMed  Google Scholar 

  48. Lieberman, M.A., Rothenberg, P., Raben, D.M., Glaser, L. 1980.Biochem. Biophys. Res. Commun. 92:696–702

    Article  PubMed  Google Scholar 

  49. Lipton, A., Klinger, I., Paul, D., Holley, R.W. 1971.Proc. Natl. Acad. Sci. USA 68:2799–2801

    PubMed  Google Scholar 

  50. Loewenstein, W.R. 1979.Biochim. Biophys. Acta 560:1–65

    PubMed  Google Scholar 

  51. Lucas, C.A., Edgar, D., Thoenen, H. 1979.Exp. Cell Res. 121:79–86

    Article  PubMed  Google Scholar 

  52. McClain, D.A., D'Eustachio, P., Edelman, G.M. 1977.Proc. Natl. Acad. Sci. USA 74:666–670

    PubMed  Google Scholar 

  53. McClain, D.A., Edelman, G.M. 1980.Proc. Natl. Acad. Sci. USA 77:2748–2752

    PubMed  Google Scholar 

  54. Mintz, G., Glaser, L. 1978.J. Cell Biol. 79:132–137

    Article  PubMed  Google Scholar 

  55. Moya, F., Glaser, L. 1980.J. Biol. Chem. 255:3258–3260

    PubMed  Google Scholar 

  56. Moya, F., Silbert, D.F., Glaser, L. 1979.Biochim. Biophys. Acta 550:485–499

    PubMed  Google Scholar 

  57. Munson, R., Jr., Westermark, B., Glaser, L. 1979.Proc. Natl. Acad. Sci. USA 76:6425–6429

    PubMed  Google Scholar 

  58. Natraj C.V., Datta, P. 1978.Proc. Natl. Acad. Sci. USA 75:6115–6119

    PubMed  Google Scholar 

  59. O'Neill, C.H., Riddle, P.N., Jordan, P.W. 1979.Cell 16:909–918

    PubMed  Google Scholar 

  60. Otto, A.M., Zumbe, A., Gibson, L., Kubler, A.-M., Jimenez de Asua, L. 1979.Proc. Natl. Acad. Sci. USA 76:6435–6438

    PubMed  Google Scholar 

  61. Pairault, J., Green, H. 1979.Proc Natl. Acad. Sci. USA 76:5138–5142

    PubMed  Google Scholar 

  62. Pardee, A.B. 1974.Proc. Natl. Acad. Sci. USA 71:1286–1290

    PubMed  Google Scholar 

  63. Pardee, A.B. 1978.J. Cell. Physiol. 95:383–386

    PubMed  Google Scholar 

  64. Pardee, A.B., Dubrow, R., Hamlin, J.C., Kletzien, R.F. 1978.Annu. Rev. Biochem. 47:715–750

    Article  PubMed  Google Scholar 

  65. Pariser, R.J., Cunningham, D.D. 1971.J. Cell Biol. 49:525–529

    Article  Google Scholar 

  66. Patrick, J., McMillan, J., Wolfson, H., O'Brien, I.C. 1977.J. Biol. Chem. 252:2143–2153

    PubMed  Google Scholar 

  67. Pfeiffer, S.E., Herschman, H.R., Lightbody, J., Sato, G. 1970.J. Cell. Physiol. 75:329–340

    Article  PubMed  Google Scholar 

  68. Pouyssegur, J.M., Pastan, I. 1976.Proc. Natl. Acad. Sci. USA 73:544–548

    PubMed  Google Scholar 

  69. Pouyssegur, J., Willingham, M., Pastan, I. 1977.Proc. Natl. Acad. Sci. USA 74:243–247

    PubMed  Google Scholar 

  70. Raben, D., Lieberman, M.A., Glaser, L. 1981.J. Cell. Physiol. (in press)

  71. Robinson, J.H., Smith, J.A. 1976.J. Cell. Physiol 89:111–122

    Article  PubMed  Google Scholar 

  72. Rosen, S.D., Barondes, S.H. 1977.In: Specificity of Embryological Interactions. D.R. Garrod, editors. pp. 235–264. Chapman and Hall, London

    Google Scholar 

  73. Rosen, S.D., Reitherman, R.W., Barondes, S.H. 1975.Exp. Cell Res. 95:159–166

    Article  PubMed  Google Scholar 

  74. Rozengurt, E. 1979.In: Hormones and Cell Culture. G. Sato and R. Ross editors. pp. 773–788. Cold Spring Harbor Laboratory, New York

    Google Scholar 

  75. Rubin, A.H., Sanui, H. 1979.In: Hormones and Cell Culture. G. Sato and R. Ross editors. pp 741–750. Cold Spring Harbor Laboratory, New York

    Google Scholar 

  76. Rudland, P.S., Jimenez de Asua, L. 1979.Biochim. Biophys. Acta 560:91–133

    PubMed  Google Scholar 

  77. Salzer, J.L., Bunge, R.P. 1980.J. Cell Biol. 84:739–752

    Article  PubMed  Google Scholar 

  78. Salzer, J.L., Bunge, R.P., Glaser L. 1980.J. Cell Biol. 84:767–778

    Article  PubMed  Google Scholar 

  79. Salzer, J.L., Williams, A.K., Glaser, L., Bunge, R.P. 1980.J. Cell Biol. 84:753–766

    Article  PubMed  Google Scholar 

  80. Santala, R., Gottlieb, D.I. Littman, D., Glaser, L. 1977.J. Biol. Chem. 252:7625–7634

    PubMed  Google Scholar 

  81. Scher, C.D., Shepard, R.D., Antoniades, H.N., Stiles, C.D. 1979.Biochim. Biophys. Acta 560:217–241

    PubMed  Google Scholar 

  82. Schnell, E., Earles, B.J., Breaux, C., Lennarz, W.J. 1977.J. Cell Biol. 72:35–46

    Article  PubMed  Google Scholar 

  83. Schubert, D., Harris, A.J., Devine, C.E., Heinemann, S. 1973.J. Cell Biol. 61:398–413

    Article  Google Scholar 

  84. Schultz, L., Mora, P.T. 1968.J. Cell. Physiol. 71:1–6

    Article  PubMed  Google Scholar 

  85. Seher, J.-P., Adam, G. 1978.Z. Naturforsch. 33c:739–743

    Google Scholar 

  86. Sorrentino, J.M., Brankow, D.W., Herschman, H.R. 1979.J. Cell Biol. 83:246a

    Google Scholar 

  87. Sorrentino, J.M., Herschman, H.R. 1980.J. Supramol. Struct. Suppl. 4:150

    Google Scholar 

  88. Steck, P.A., Voss, P.G., Wang, J.L. 1979.J. Cell Biol. 83:562–575

    Article  PubMed  Google Scholar 

  89. Stoker, M.G.P. 1973.Nature (London) 246:200–203

    Google Scholar 

  90. Stocker, M., O'Neill, C., Berryman, S., Waxman, V. 1968.Int. J. Cancer 3:683–686

    PubMed  Google Scholar 

  91. Stoker, M., Piggott, D. 1974.Cell 3:207–215

    Article  PubMed  Google Scholar 

  92. Thomopoulus, P., Roth, J., Lovelace, E., Pastan, I. 1976.Cell 8:417–423

    Article  PubMed  Google Scholar 

  93. Trash, C.R., Cunningham, D.D. 1975.J. Cell. Physiol. 86:301–310

    Article  PubMed  Google Scholar 

  94. Todaro, G.J., Green, H. 1963.J. Cell Biol. 17:299–313

    Article  PubMed  Google Scholar 

  95. Todaro G., Green, H., Goldberg, B.D. 1964.Proc. Natl. Acad. Sci. USA 51:66–73

    PubMed  Google Scholar 

  96. Umbreit, J., Roseman, S. 1975.J. Biol. Chem. 250:9360–9368

    PubMed  Google Scholar 

  97. Ushiro, H., Cohen, S. 1980.J. Biol. Chem. 255:8363–8365

    PubMed  Google Scholar 

  98. Vacquier, V.D., Moy, G.W. 1977.Proc. Natl. Acad. Sci USA 74:2456–2460

    PubMed  Google Scholar 

  99. Vacquier, V.D., Moy, G.W. 1978.In: Cell Reproduction. ICN-UCLA Symp. Mol. Cell Biol. G.R. Dirksen, D. Prescott and C.F. Fox, editors. Vol. 12. Academic Press, New York

    Google Scholar 

  100. Vogel, A., Ross, R., Raines, E. 1980.J. Cell Biol. 85:377–385

    Article  PubMed  Google Scholar 

  101. Weigel, P.H., Schmell, E., Lee, Y.C., Roseman, S. 1978.J. Biol. Chem. 253:330–333

    PubMed  Google Scholar 

  102. Westermark, B. 1971.Exp. Cell Res. 69:259–264

    Article  PubMed  Google Scholar 

  103. Westermark, B. 1977.Proc. Natl. Acad. Sci. USA 74:1619–1621

    PubMed  Google Scholar 

  104. Whittenberger, B., Glaser, L. 1977.Proc. Natl. Acad. Sci. USA 74:2251–2255

    PubMed  Google Scholar 

  105. Whittenberger, B., Glaser, L. 1978.Nature (London) 272:821–823

    Google Scholar 

  106. Whittenberger, B., Raben, D., Glaser, L. 1979.J. Supramol. Struct. 10:307–327

    Article  PubMed  Google Scholar 

  107. Whittenberger, B., Raben, D., Lieberman, M.A., Glaser, L. 1978.Proc. Natl. Acad. Sci. USA 75:5457–5461

    PubMed  Google Scholar 

  108. Wrann, M., Fox, C.F., Ross, R. 1980.Science 210:1363–1365

    PubMed  Google Scholar 

  109. Yamada, K.M., Olden, K. 1978.Nature (London) 275:179–184

    Google Scholar 

  110. Yeh, J., Fisher, H.W. 1969. A diffusible factor which sustains contact inhibition of replication.J. Cell Biol. 40:382–388

    Article  PubMed  Google Scholar 

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Lieberman, M.A., Glaser, L. Density-dependent regulation of cell growth: An example of a cell-cell recognition phenomenon. J. Membrain Biol. 63, 1–11 (1981). https://doi.org/10.1007/BF01969440

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