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Mol Biol Cell. 1993 Sep; 4(9): 953–961.
PMCID: PMC275725

The extracellular matrix as a cell survival factor.


Programmed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. In many cases, PCD is induced by the withdrawal of specific hormones or growth factors that function as survival factors. In this study, we have investigated the potential role of the extracellular matrix (ECM) as a cell survival factor. Our results indicate that in the absence of any ECM interactions, human endothelial cells rapidly undergo PCD, as determined by cell morphology, nuclei fragmentation, DNA degradation, protein cross-linking, and the expression of the PCD-specific gene TRPM-2. PCD was blocked by plating cells on an immobilized integrin beta 1 antibody but not by antibodies to either the class I histocompatibility antigen (HLA) or vascular cell adhesion molecule-1 (VCAM-1), suggesting that integrin-mediated signals were required for maintaining cell viability. Treatment of the cells in suspension with the tyrosine phosphatase inhibitor sodium orthovanadate also blocked PCD. When other cell types were examined, some, but not all, underwent rapid cell death when deprived of adhesion to the ECM. These results suggest that in addition to regulating cell growth and differentiation, the ECM also functions as a survival factor for many cell types.

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  • Araki S, Shimada Y, Kaji K, Hayashi H. Apoptosis of vascular endothelial cells by fibroblast growth factor deprivation. Biochem Biophys Res Commun. 1990 May 16;168(3):1194–1200. [PubMed]
  • Bandyk MG, Sawczuk IS, Olsson CA, Katz AE, Buttyan R. Characterization of the products of a gene expressed during androgen-programmed cell death and their potential use as a marker of urogenital injury. J Urol. 1990 Feb;143(2):407–413. [PubMed]
  • Bardon S, Vignon F, Montcourrier P, Rochefort H. Steroid receptor-mediated cytotoxicity of an antiestrogen and an antiprogestin in breast cancer cells. Cancer Res. 1987 Mar 1;47(5):1441–1448. [PubMed]
  • Bettuzzi S, Hiipakka RA, Gilna P, Liao ST. Identification of an androgen-repressed mRNA in rat ventral prostate as coding for sulphated glycoprotein 2 by cDNA cloning and sequence analysis. Biochem J. 1989 Jan 1;257(1):293–296. [PMC free article] [PubMed]
  • Burridge K, Turner CE, Romer LH. Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J Cell Biol. 1992 Nov;119(4):893–903. [PMC free article] [PubMed]
  • BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. [PMC free article] [PubMed]
  • Buttyan R, Olsson CA, Pintar J, Chang C, Bandyk M, Ng PY, Sawczuk IS. Induction of the TRPM-2 gene in cells undergoing programmed death. Mol Cell Biol. 1989 Aug;9(8):3473–3481. [PMC free article] [PubMed]
  • Compton MM. A biochemical hallmark of apoptosis: internucleosomal degradation of the genome. Cancer Metastasis Rev. 1992 Sep;11(2):105–119. [PubMed]
  • Daniels K, Solursh M. Modulation of chondrogenesis by the cytoskeleton and extracellular matrix. J Cell Sci. 1991 Oct;100(Pt 2):249–254. [PubMed]
  • Duke RC, Cohen JJ. IL-2 addiction: withdrawal of growth factor activates a suicide program in dependent T cells. Lymphokine Res. 1986 Fall;5(4):289–299. [PubMed]
  • Ellis RE, Yuan JY, Horvitz HR. Mechanisms and functions of cell death. Annu Rev Cell Biol. 1991;7:663–698. [PubMed]
  • Ernsberger U, Edgar D, Rohrer H. The survival of early chick sympathetic neurons in vitro is dependent on a suitable substrate but independent of NGF. Dev Biol. 1989 Oct;135(2):250–262. [PubMed]
  • Fesus L, Thomazy V, Falus A. Induction and activation of tissue transglutaminase during programmed cell death. FEBS Lett. 1987 Nov 16;224(1):104–108. [PubMed]
  • Fort P, Marty L, Piechaczyk M, el Sabrouty S, Dani C, Jeanteur P, Blanchard JM. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. [PMC free article] [PubMed]
  • Guan JL, Shalloway D. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature. 1992 Aug 20;358(6388):690–692. [PubMed]
  • Guan JL, Trevithick JE, Hynes RO. Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein. Cell Regul. 1991 Nov;2(11):951–964. [PMC free article] [PubMed]
  • Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. [PubMed]
  • Jenne DE, Tschopp J. Clusterin: the intriguing guises of a widely expressed glycoprotein. Trends Biochem Sci. 1992 Apr;17(4):154–159. [PubMed]
  • Juliano RL, Haskill S. Signal transduction from the extracellular matrix. J Cell Biol. 1993 Feb;120(3):577–585. [PMC free article] [PubMed]
  • Kalcheim C, Barde YA, Thoenen H, Le Douarin NM. In vivo effect of brain-derived neurotrophic factor on the survival of developing dorsal root ganglion cells. EMBO J. 1987 Oct;6(10):2871–2873. [PMC free article] [PubMed]
  • Kornberg LJ, Earp HS, Turner CE, Prockop C, Juliano RL. Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of beta 1 integrins. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8392–8396. [PMC free article] [PubMed]
  • Kyprianou N, Isaacs JT. Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology. 1988 Feb;122(2):552–562. [PubMed]
  • Léger JG, Montpetit ML, Tenniswood MP. Characterization and cloning of androgen-repressed mRNAs from rat ventral prostate. Biochem Biophys Res Commun. 1987 Aug 31;147(1):196–203. [PubMed]
  • McConkey DJ, Hartzell P, Nicotera P, Orrenius S. Calcium-activated DNA fragmentation kills immature thymocytes. FASEB J. 1989 May;3(7):1843–1849. [PubMed]
  • Miekka SI, Ingham KC, Menache D. Rapid methods for isolation of human plasma fibronectin. Thromb Res. 1982 Jul 1;27(1):1–14. [PubMed]
  • Rotello RJ, Hocker MB, Gerschenson LE. Biochemical evidence for programmed cell death in rabbit uterine epithelium. Am J Pathol. 1989 Mar;134(3):491–495. [PMC free article] [PubMed]
  • Sahaphong S, Trump BF. Studies of cellular injury in isolated kidney tubules of the flounder. V. Effects of inhibiting sulfhydryl groups of plasma membrane with the organic mercurials PCMB (parachloromercuribenzoate) and PCMB (parachloromercuribenzenesulfonate). Am J Pathol. 1971 May;63(2):277–298. [PMC free article] [PubMed]
  • Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB, Parsons JT. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192–5196. [PMC free article] [PubMed]
  • Schwartz MA. Transmembrane signalling by integrins. Trends Cell Biol. 1992 Oct;2(10):304–308. [PubMed]
  • Schwartz MA. Signaling by integrins: implications for tumorigenesis. Cancer Res. 1993 Apr 1;53(7):1503–1506. [PubMed]
  • Shimizu Y, Shaw S. Lymphocyte interactions with extracellular matrix. FASEB J. 1991 Jun;5(9):2292–2299. [PubMed]
  • Strange R, Li F, Saurer S, Burkhardt A, Friis RR. Apoptotic cell death and tissue remodelling during mouse mammary gland involution. Development. 1992 May;115(1):49–58. [PubMed]
  • Talhouk RS, Bissell MJ, Werb Z. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol. 1992 Sep;118(5):1271–1282. [PMC free article] [PubMed]
  • Talhouk RS, Chin JR, Unemori EN, Werb Z, Bissell MJ. Proteinases of the mammary gland: developmental regulation in vivo and vectorial secretion in culture. Development. 1991 Jun;112(2):439–449. [PMC free article] [PubMed]
  • Wyllie AH. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. [PubMed]
  • Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. [PubMed]

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