Radiotherapy & Oncology
Volume 92, Issue 3 , Pages 362-370 , September 2009

Caveolin-1 mediated radioresistance of 3D grown pancreatic cancer cells

  • Stephanie Hehlgans

      Affiliations

    • OncoRay – Center for Radiation Research in Oncology, Dresden University of Technology, Dresden, Germany
    • ,
  • Iris Eke

      Affiliations

    • OncoRay – Center for Radiation Research in Oncology, Dresden University of Technology, Dresden, Germany
    • ,
  • Katja Storch

      Affiliations

    • OncoRay – Center for Radiation Research in Oncology, Dresden University of Technology, Dresden, Germany
    • ,
  • Michael Haase

      Affiliations

    • Department Children’s Surgery, Dresden University of Technology, Dresden, Germany
    • Department of Pathology, Dresden University of Technology, Dresden, Germany
    • ,
  • Gustavo B. Baretton

      Affiliations

    • Department of Pathology, Dresden University of Technology, Dresden, Germany
    • ,
  • Nils Cordes

      Affiliations

    • OncoRay – Center for Radiation Research in Oncology, Dresden University of Technology, Dresden, Germany
    • Corresponding Author InformationCorresponding author. Address: OncoRay – Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstrasse 74/PF 86, 01307 Dresden, Germany.

Received 22 April 2009 ,Revised 30 June 2009 ,Accepted 3 July 2009.

References 

  1. Lee SW, Reimer CL, Oh P, Campbell DB, Schnitzer JE. Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells. Oncogene. 1998;16:1391–1397
  2. Ando T, Ishiguro H, Kimura M, et al. The overexpression of caveolin-1 and caveolin-2 correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma. Oncol Rep. 2007;18:601–609
  3. Tanase CP. Caveolin-1: a marker for pancreatic cancer diagnosis. Expert Rev Mol Diagn. 2008;8:395–404
  4. Quest AF, Gutierrez-Pajares JL, Torres VA. Caveolin-1: an ambiguous partner in cell signalling and cancer. J Cell Mol Med. 2008;12:1130–1150
  5. Williams TM, Lisanti MP. The Caveolin genes: from cell biology to medicine. Ann Med. 2004;36:584–595
  6. Patel HH, Murray F, Insel PA. Caveolae as organizers of pharmacologically relevant signal transduction molecules. Annu Rev Pharmacol Toxicol. 2008;48:359–391
  7. Shatz M, Liscovitch M. Caveolin-1: a tumor-promoting role in human cancer. Int J Radiat Biol. 2008;84:177–189
  8. Li L, Ren CH, Tahir SA, Ren C, Thompson TC. Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A. Mol Cell Biol. 2003;23:9389–9404
  9. Zhang B, Peng F, Wu D, Ingram AJ, Gao B, Krepinsky JC. Caveolin-1 phosphorylation is required for stretch-induced EGFR and Akt activation in mesangial cells. Cell Signal. 2007;19:1690–1700
  10. Wary KK, Mariotti A, Zurzolo C, Giancotti FG. A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth. Cell. 1998;94:625–634
  11. Del Pozo MA, Schwartz MA. Rac, membrane heterogeneity, caveolin and regulation of growth by integrins. Trends Cell Biol. 2007;17:246–250
  12. Hynes RO. The emergence of integrins: a personal and historical perspective. Matrix Biol. 2004;23:333–340
  13. Frisch SM, Ruoslahti E. Integrins and anoikis. Curr Opin Cell Biol. 1997;9:701–706
  14. Degterev A, Yuan J. Expansion and evolution of cell death programmes. Nat Rev Mol Cell Biol. 2008;9:378–390
  15. Schwab W, Kasper M, Gavlik JM, Schulze E, Funk RH, Shakibaei M. Characterization of caveolins from human knee joint cartilage: expression of caveolin-1, -2, and -3 in chondrocytes and association with integrin beta1. Histochem Cell Biol. 2000;113:221–225
  16. Wickstrom SA, Alitalo K, Keski-Oja J. Endostatin associates with integrin alpha5beta1 and caveolin-1, and activates Src via a tyrosyl phosphatase-dependent pathway in human endothelial cells. Cancer Res. 2002;62:5580–5589
  17. Li J, Hassan GS, Williams TM, et al. Loss of caveolin-1 causes the hyper-proliferation of intestinal crypt stem cells, with increased sensitivity to whole body gamma-radiation. Cell Cycle. 2005;4:1817–1825
  18. Cordes N, Frick S, Brunner TB, et al. Human pancreatic tumor cells are sensitized to ionizing radiation by knockdown of caveolin-1. Oncogene. 2007;26:6851–6862
  19. Hodkinson PS, Elliott T, Wong WS, et al. ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell lung cancer cells through beta1 integrin-dependent activation of PI3-kinase. Cell Death Differ. 2006;13:1776–1788
  20. Eke I, Sandfort V, Mischkus A, Baumann M, Cordes N. Antiproliferative effects of EGFR tyrosine kinase inhibition and radiation-induced genotoxic injury are attenuated by adhesion to fibronectin. Radiother Oncol. 2006;80:178–184
  21. Hehlgans S, Eke I, Deuse Y, Cordes N. Integrin-linked kinase: dispensable for radiation survival of three-dimensionally cultured fibroblasts. Radiother Oncol. 2008;86:329–335
  22. Fiucci G, Ravid D, Reich R, Liscovitch M. Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells. Oncogene. 2002;21:2365–2375
  23. Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 2001;61:3550–3555
  24. Cordes N, Seidler J, Durzok R, Geinitz H, Brakebusch C. Beta1-integrin-mediated signaling essentially contributes to cell survival after radiation-induced genotoxic injury. Oncogene. 2006;25:1378–1390
  25. Rothkamm K, Lobrich M. Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci USA. 2003;100:5057–5062
  26. Eke I, Sandfort V, Storch K, Baumann M, Roper B, Cordes N. Pharmacological inhibition of EGFR tyrosine kinase affects ILK-mediated cellular radiosensitization in vitro. Int J Radiat Biol. 2007;83:793–802
  27. Haase M, Gmach CC, Eke I, Hehlgans S, Baretton GB, Cordes N. Expression of integrin-linked kinase is increased in differentiated cells. J Histochem Cytochem. 2008;56:819–829
  28. Estrugo D, Fischer A, Hess F, Scherthan H, Belka C, Cordes N. Ligand bound beta1 integrins inhibit procaspase-8 for mediating cell adhesion-mediated drug and radiation resistance in human leukemia cells. PLoS ONE. 2007;2:e269
  29. Barar J, Campbell L, Hollins AJ, et al. Cell selective glucocorticoid induction of caveolin-1 and caveolae in differentiating pulmonary alveolar epithelial cell cultures. Biochem Biophys Res Commun. 2007;359:360–366
  30. Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer. 2008;8:545–554
  31. Sawyers C. Targeted cancer therapy. Nature. 2004;432:294–297
  32. Krause M, Zips D, Thames HD, Kummermehr J, Baumann M. Preclinical evaluation of molecular-targeted anticancer agents for radiotherapy. Radiother Oncol. 2006;80:112–122
  33. Weaver VM, Fischer AH, Peterson OW, Bissell MJ. The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay. Biochem Cell Biol. 1996;74:833–851
  34. Debnath J, Brugge JS. Modelling glandular epithelial cancers in three-dimensional cultures. Nat Rev Cancer. 2005;5:675–688
  35. Bissell MJ. Modelling molecular mechanisms of breast cancer and invasion: lessons from the normal gland. Biochem Soc Trans. 2007;35:18–22
  36. Wolters NM, MacKeigan JP. From sequence to function: using RNAi to elucidate mechanisms of human disease. Cell Death Differ. 2008;15:809–819
  37. Stupack DG, Puente XS, Boutsaboualoy S, Storgard CM, Cheresh DA. Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins. J Cell Biol. 2001;155:459–470
  38. Lee H, Volonte D, Galbiati F, et al. Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: identification of a c-Src/Cav-1/Grb7 signaling cassette. Mol Endocrinol. 2000;14:1750–1775
  39. Park CC, Zhang HJ, Yao ES, Park CJ, Bissell MJ. Beta1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts. Cancer Res. 2008;68:4398–4405
  40. Cordes N, Hansmeier B, Beinke C, Meineke V, van Beuningen D. Irradiation differentially affects substratum-dependent survival, adhesion, and invasion of glioblastoma cell lines. Br J Cancer. 2003;89:2122–2132

PII: S0167-8140(09)00393-4

doi: 10.1016/j.radonc.2009.07.004

Radiotherapy & Oncology
Volume 92, Issue 3 , Pages 362-370 , September 2009

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