DOI QR코드

DOI QR Code

Calpeptin Prevents Malignant Pleural Mesothelioma Cell Proliferation via the Angiopoietin-1/Tie-2 System

  • Tabata, Chiharu (Cancer Center, Hyogo College of Medicine) ;
  • Tabata, Rie (Department of Hematology and Rheumatology, Saiseikai-Noe Hospital) ;
  • Nakano, Takashi (Cancer Center, Hyogo College of Medicine)
  • Published : 2016.07.01

Abstract

Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. Progress in the development of therapeutic strategies for MPM has been limited. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)-1 and Tie-2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang-1-induced proliferation of MPM cells through an NF-kB dependent pathway, which may be the mechanism underlying the preventive effects of calpeptin on the growth of MPM cells. These results suggest potential clinical use of calpeptin for the treatment of MPM.

Keywords

Calpeptin;mesothelioma;cell proliferation;Ang-1/Tie-2 mRNA

Acknowledgement

Supported by : KAKENHI

References

  1. American Thoracic Society/European Respiratory Society (2002). International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med, 165, 277-304. https://doi.org/10.1164/ajrccm.165.2.ats01
  2. Coultas DB, Zumwalt RE, Black WC, Sobonya RE (1994). The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med, 150, 967-72. https://doi.org/10.1164/ajrccm.150.4.7921471
  3. Edwards JG, Swinson DE, Jones JL, et al (2003). Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma. Chest, 124, 1916-23. https://doi.org/10.1378/chest.124.5.1916
  4. Goll DE, Thompson VF, Li H, Wei W, Cong J (2003). The calpain system. Physiol Rev, 83, 731-801. https://doi.org/10.1152/physrev.00029.2002
  5. Gross TJ, Hunninghake GW (2001). Idiopathic pulmonary fibrosis. N Engl J Med, 345, 517-25. https://doi.org/10.1056/NEJMra003200
  6. Jain RK (2003). Molecular regulation of vessel maturation. Nat Med, 9, 685-93. https://doi.org/10.1038/nm0603-685
  7. Nowak AK, Lake RA, Kindler HL, Robinson BW (2002). New approaches for mesothelioma: biologics, vaccines, gene therapy, and other novel agents. Semin Oncol, 29, 82-96. https://doi.org/10.1053/sonc.2002.30234
  8. Robinson BW, Musk AW, Lake RA (2005). Malignant mesothelioma. Lancet, 366, 397-408. https://doi.org/10.1016/S0140-6736(05)67025-0
  9. Robinson BW, Lake RA (2005). Advances in malignant mesothelioma. N Engl J Med, 353, 1591-603. https://doi.org/10.1056/NEJMra050152
  10. Selikoff IJ, Hammond EC, Seidman H (1980). Latency of asbestos disease among insulation workers in the united states and canada. Cancer, 15, 2736-40.
  11. Sterman DH, Kaiser LR, Albelda SM (1999). Advances in the treatment of malignant pleural mesothelioma. Chest, 116, 504-20. https://doi.org/10.1378/chest.116.2.504
  12. Sullivan DE, Ferris M, Pociask D, Brody AR (2005). Tumor necrosis factor-alpha induces transforming growth factorbeta1 expression in lung fibroblasts through the extracellular signal-regulated kinase pathway. Am J Respir Cell Mol Biol, 32, 342-9. https://doi.org/10.1165/rcmb.2004-0288OC
  13. Tabata C, Kubo H, Tabata R, et al (2006). All-trans retinoic acid modulates radiation-induced proliferation of lung fibroblasts via IL-6/IL-6R system. Am J Physiol Lung Cell Mol Physiol, 290, 597-606. https://doi.org/10.1152/ajplung.00282.2005
  14. Tabata C, Kadokawa Y, Tabata R, et al (2006). All-trans-Retinoic Acid Prevents Radiation- or Bleomycin-induced Pulmonary Fibrosis. Am J Respir Crit Care Med, 174, 1352-60. https://doi.org/10.1164/rccm.200606-862OC
  15. Tabata C, Tabata R, Kadokawa Y, et al (2007). Thalidomide prevents bleomycin-induced pulmonary fibrosis in mice. J Immunol, 179, 708-14. https://doi.org/10.4049/jimmunol.179.1.708
  16. Tabata C, Tabata R, Nakano T (2010). The calpain inhibitor calpeptin prevents bleomycin-induced pulmonary fibrosis in mice. Clin Exp Immunol, 162, 560-7. https://doi.org/10.1111/j.1365-2249.2010.04257.x
  17. Tabata C, Hirayama N, Tabata R, et al (2010). A novel clinical role for angiopoietin-1 in malignant pleural mesothelioma. Eur Respir J, 36, 1099-105. https://doi.org/10.1183/09031936.00154009
  18. Thurston G, Rudge JS, Ioffe E, et al (2000). Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med, 6, 460-63. https://doi.org/10.1038/74725
  19. Vogelzang NJ, Rusthoven JJ, Symanowski J, Sporn MB, Roberts AB (2003). Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol, 21, 2636-44. https://doi.org/10.1200/JCO.2003.11.136
  20. Wagner JC, Sleggs CA, Marchand P (1960). Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med, 17, 260-71.
  21. Yancopoulos GD, Davis S, Gale NW, et al (2000). Vascularspecific growth factors and blood vessel formation. Nature, 407, 242-8. https://doi.org/10.1038/35025215
  22. Yang H, Bocchetta M, Kroczynska B, et al (2006). TNF-alpha inhibits asbestos-induced cytotoxicity via a NF-kappaB-dependent pathway, a possible mechanism for asbestosinduced oncogenesis. Proc Natl Acad Sci USA, 103, 10397-402. https://doi.org/10.1073/pnas.0604008103