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Integrin-mediated entry into S phase of human gastric adenocarcinoma cells

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Abstract

The integrins are a family of integral membrane receptors that participate in binding to various extracellular and cell surface proteins during adhesion, migration, and homing of normal and neoplastic cells. In this study, we characterized the involvement of integrins in mediating the growth of an adhesion-dependent gastric adenocarcinoma line, ST2. This line was distinguished and selected for study based on its inability to grow when suspended in soft agar or plated on poly(2-hydroxyethyl methacrylate)-coated dishes. ST2 cells arrested in G0/G1 of the cell cycle when deprived of adhesion to substrate. Using purified matrix components, collagen was found to be highly active in promoting β1 integrin-mediated cell attachment and spreading. Subsequent to spreading on collagen, the cells were released from G0/G1 block and progressed into S phase. Monoclonal antibodies to α2 or β1 integrin blocked the reinduction of both cell spreading and entry into S phase. These studies suggest that during the metastatic process, integrin receptor interaction with the insoluble matrix may be an important step leading to proliferation of some tumors.

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References

  1. Albelda, SM and Buck, CA, 1990, Integrins and other cell adhesion molecules.FASEB J,4, 2868–80.

    Google Scholar 

  2. Ruoslahti, E, 1991, Integrins.J Clin Invest,87, 1–5.

    Google Scholar 

  3. Hynes, RO, 1992, Integrins: versatility, modulation, and signaling in cell adhesion.Cell,69, 11–25.

    Google Scholar 

  4. Palmer, EL, Ruegs, C, Ferrando, R, Pytela, R and Sheppard, D, 1993, Sequence and tissue distribution of the integrin α9 subunit, a novel partner of β1 that is widely distributed in epithelia and muscle.J Cell Biol,123, 1289–96.

    Google Scholar 

  5. Juliano, RL and Haskill, S, 1993, Signal transduction from the extracellular matrix.J Cell Biol,120, 577–85.

    Google Scholar 

  6. Ruoslahti, E and Giancotti, FG, 1989, Integrins and tumor invasion.Cancer Cells,1, 119–25.

    Google Scholar 

  7. Zetter, BR, 1993, Adhesion molecules in tumor metastasis.Seminars in Cancer Biol,4, 219–29.

    Google Scholar 

  8. Chan, BM, Matsuura, N, Takada, Y, Zetter, BR and Hemler, ME, 1991,In vitro andin vivo consequences of VLA-2 expression on rhabdomyosarcoma cells.Science,251, 1600–2.

    Google Scholar 

  9. Paavonen, T, Tiisala, S, Majuri, M-L, Bohling, T and Renkonen, R, 1994,In vivo evidence of the role of α4β1-VCAM-1 interaction in sarcoma, but not in carcinoma extravasation.Int J Cancer,58, 298–302.

    Google Scholar 

  10. Roossien, FF, de Rijk, D, Bikker, A and Roos, E, 1989, Involvement of LFA-1 in lymphoma invasion and metastasis demonstrated with LFA-1 deficient mutants.J Cell Biol,108, 1979–85.

    Google Scholar 

  11. Wittelsberger, SC, Kleene, K and Penman, S, 1981, Progressive loss of shape responsive metabolic controls in cells with increasingly transformed phenotype.Cell,24, 859–66.

    Google Scholar 

  12. Fidler, IJ, 1990, Host and tumour factors in cancer metastasis.Eur J Clin Invest,20, 481–6.

    Google Scholar 

  13. Nicolson, GL, 1993, Cancer progression and growth: relationship of paracrine and autocrine growth mechanisms to organ preference metastasis.Exp Cell Res,204, 171–80.

    Google Scholar 

  14. Auvinen, M, Passinen, A, Andersson, LC and Holtta, E, 1992, Ornithine decarboxylase is critical for cell transformation.Nature,360, 355–8.

    Google Scholar 

  15. Pathak, S, 1976, Chromosome banding techniques.J Reprod Med,17, 25–8.

    Google Scholar 

  16. Hopwood, VL and Pathak, S, 1994, Improved quality of Giemsa banding by the use of trypsin concentrate.Am Biotechnol Lab,12, 52–3.

    Google Scholar 

  17. Bednarczyk, JL, Wygant, JN, Szabo, MC,et al. 1993, Homotypic leukocyte aggregation triggered by a monoclonal antibody specific for a novel epitope expressed by the integrin β1 subunit: conversion of a nonresponsive cell by transfecting human integrin α4 subunit cDNA.J Cell Biochem,51, 465–78.

    Google Scholar 

  18. Bednarczyk, JL, Szabo, MC, Wygant, JN, Lazarovits, A and McIntyre, BW, 1994, Identification of a combinatorial epitope expressed by the integrin α4β1 heterodimer involved in the regulation of cell adhesion.J Biol Chem,269, 8348–54.

    Google Scholar 

  19. Kappler, J, Kubo, R, Haskins, K,et al. 1983, The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man. V. Identification of constant and variable peptides.Cell,35, 295–302.

    Google Scholar 

  20. Bednarczyk, JL, Szabo, MC and McIntyre, BW, 1992, Post-translational processing of the leukocyte integrin α4β1.J Biol Chem,35, 25274–81.

    Google Scholar 

  21. Luque, A, Sanchez-Madrid, F and Cabanas, C, 1994, Functional regulation of the human integrin VLA-1 (CD49a/CD29) by divalent cations and stimulatory β1 antibodies.FEBS Lett,346, 278–84.

    Google Scholar 

  22. Hemler, ME, Sanchez-Madrid, F, Flotte, TJ,et al. 1984, Glycoprotein of 210,000 and 130,000 M.W. on activated T cells: cell distribution and antigenic relation to components on resting cells and cell lines.J Immunol,132, 3011–18.

    Google Scholar 

  23. Folkman, J and Moscona, A, 1978, Role of cell shape in growth control.Nature,273, 345–9.

    Google Scholar 

  24. Freedman, VH and Shin, S, 1974, Cellular tumorigenicity in nude mice: correlation with cell growth in semisolid medium.Cell,3, 355–9.

    Google Scholar 

  25. Sauter, G, Haley, J, Chew, K,et al. 1994, Epidermalgrowth-factor-receptor expression is associated with rapid tumor proliferation in bladder cancer.Int J Cancer,57, 508–14.

    Google Scholar 

  26. Helseth, E, Brogger, A, Dalen, A,et al. 1990, Polysomy of chromosome 7 is associated with amplification and overexpression of the EGF-receptor gene in human carcinoma cell line derived from a brain metastasis.APMIS,98, 996–1004.

    Google Scholar 

  27. Schlegel, J, Merdes, A, Stumm, G,et al. 1994, Amplification of the epidermal-growth-factor-receptor gene correlates with different growth behaviour in human glioblastoma.Int J Cancer,56, 72–7.

    Google Scholar 

  28. Harris, CC, 1993, p53: at the crossroads of molecular carcinogenesis and risk assessment.Science,262, 1980–1.

    Google Scholar 

  29. Halevy, O, Michalovitz, D and Oren, M, 1990, Different tumor-derived p53 mutants exhibit distinct biological activities.Science,250, 113–16.

    Google Scholar 

  30. Pardee, AB, 1989, G1 events and regulation of cell proliferation.Science,246, 603–8.

    Google Scholar 

  31. Delwel, GO, de Melker, AA, Hogervorst, F,et al. 1994, Distinct and overlapping ligand specificities of the αAβ1 and α6Aβ1 integrins: recognition of laminin isoforms.Molec Biol Cell,5, 203–15.

    Google Scholar 

  32. Werb, Z, Tremble, PM, Behrendtsen, O, Crowley, E and Damsky, CH, 1989, Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene induction.J Cell Biol,109, 877–89.

    Google Scholar 

  33. Montgomery, AMP, Reisfeld, RA and Cheresh, DA, 1994, Integrin α4β3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen.Proc Natl Acad Sci USA,91, 8856–60.

    Google Scholar 

  34. Qian, F, Vaux, LL and Weissman, IL, 1994, Expression of the integrin a4 β1 on melanoma can inhibit the invasive stage of metastasis formation.Cell,77, 335–47.

    Google Scholar 

  35. Tahara, E, 1990, Growth factors and oncogenes in human gastrointestinal carcinomas.J Cancer Res Clin Oncol,116, 121–131.

    Google Scholar 

  36. Lemoine, NR, Jain, S, Silvestre, F,et al. 1991, Amplification and overexpression of the EGF receptor and c-erbB-2 proto-oncogenes in human stomach cancer.Br J Cancer,64, 79–83.

    Google Scholar 

  37. Spyratos, F, Delarue, JC, Andrieu, C,et al. 1990, Epidermal growth factor receptors and prognosis in primary breast cancer.Breast Cancer Res Treat,17, 83–9.

    Google Scholar 

  38. Chen, SC, Chou, CK, Wong, FH, Chang, CM and Hu, CP, 1991, Overexpression of epidermal growth factor and insulin-like growth factor-I receptors and autocrine stimulation in human esophageal carcinoma cells.Cancer Res,51, 1898–903.

    Google Scholar 

  39. Jones, GJ, Heiss, NS, Veale, RB and Thornley, AL, 1993, Amplification and expression of the TGF-alpha, EGF receptor and c-myc genes in four human oesophageal squamous cell carcinoma lines.Biosc Rep,13, 303–12.

    Google Scholar 

  40. McNamee, H, Ingber, DE and Schwartz, MA, 1993, Adhesion to fibronectin stimulates inositol lipid synthesis and enhances PDGF-induced inositol lipid breakdown.J Cell Biol,121, 673–8.

    Google Scholar 

  41. Ben-Ze'ev, A, Farmer, SR and Penman, S, 1980, Protein synthesis requires cell-surface contact while nuclear events respond to cell shape in anchorage-dependent fibroblasts.Cell,21, 365–72.

    Google Scholar 

  42. Otsuka, H and Moscovitz, M, 1975, Arrest of 3T3 cells in G1 phase in suspension culture.J Cell Physiol,87, 213–20.

    Google Scholar 

  43. Tucker, RW, Butterfield, CE and Folkman, J, 1981, Interaction of serum and cell spreading affects growth of neoplastic and non-neoplastic cells.J Supramolec Struct,15, 29–40.

    Google Scholar 

  44. Gospodarowicz, D, Delgado, D and Vlodavsky, I, 1980, Permissive effect of the extracellular matrix on cell proliferationin vitro.Proc Nat Acad Sci USA,77, 4094–8.

    Google Scholar 

  45. Burridge, K, Fath, K, Kelly, T, Nuckolls, G and Turner, C, 1988, Focal adhesion: transmembrane junctions between the extracellular matrix and the cytoskeleton.Ann Rev Cell Biol,4, 487–525.

    Google Scholar 

  46. Zachary, I and Rozengurt, E, 1992, Focal adhesion kinase (pl25FAK): a point of convergence in the action of neuropeptides, integrins, and oncogenes.Cell,71, 891–4.

    Google Scholar 

  47. Cobb, BS, Schaller, MD and Parsons, JT, 1994, Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK.Molec Cell Biol,14, 147–55.

    Google Scholar 

  48. Rodriguez Fernandez, JL, Geiger, B, Salomon, D and Ben- Ze'ev, A, 1993, Suppression of vinculin by antisense transfection confers changes in cell morphology, motility, and anchorage dependent growth of 3T3 cell.J Cell Biol,122, 1285–94.

    Google Scholar 

  49. Rodriguez Fernandez, JL, Geiger, B, Salomon, D, Sabanay, I, Zoller, M and Ben-Ze'ev, A, 1992, Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.J Cell Biol,119, 427–38.

    Google Scholar 

  50. Howlett, AR and Bissell, MJ, 1993, The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium.Epithel Cell Biol,2, 79–89.

    Google Scholar 

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Authors and Affiliations

  1. Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Taturo Udagawa & Bradley W. McIntyre

  2. Cell Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Vicki L. Hopwood & Sen Pathak

Authors
  1. Taturo Udagawa
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  2. Vicki L. Hopwood
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  3. Sen Pathak
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  4. Bradley W. McIntyre
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Udagawa, T., Hopwood, V.L., Pathak, S. et al. Integrin-mediated entry into S phase of human gastric adenocarcinoma cells. Clin Exp Metast 13, 427–438 (1995). https://doi.org/10.1007/BF00118182

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  • DOI: https://doi.org/10.1007/BF00118182

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