DOI QR코드

DOI QR Code

Molecular and Circulatory Expression of Insulin Growth Factors in Indian Females with Advanced Cervical Cancer

  • Sharma, Manoj (Department of Radiotherapy, Maulana Azad Medical College and Associated Lok Nayak Hospital) ;
  • Satyam, Abhigyan (Department of Biochemistry, All India Institute of Medical Sciences) ;
  • Abhishek, Ashu (Department of Radiotherapy, Maulana Azad Medical College and Associated Lok Nayak Hospital) ;
  • Khan, Rehan (Department of Biochemistry, All India Institute of Medical Sciences) ;
  • Rajappa, Medha (Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research) ;
  • Sharma, Alpana (Department of Biochemistry, All India Institute of Medical Sciences)
  • Published : 2012.12.31

Abstract

Background: Recent studies have demonstrated an association between insulin growth factor (IGF) and insulin growth factor binding protein-3 (IGFBP-III) serum levels and increased risk for various cancers. However, little information is available on clinical implications of the IGF system in Indian patients with cervical cancer. This study explored associations by analyzing their expression profiles in cervical cancer cases. Materials and Methods: Totals of 50 patients with advanced cervical cancer and 40 healthy controls were enrolled. Human papillomavirus (HPV) and cervical biopsy sample were obtained from all participating women. Circulatory levels were estimated by ELISA and the tissue expression was assessed using RT-PCR and Western blotting. Results: Levels of IGF-I and II showed significant increase whereas IGFBP-III showed significant decline in all patients as compared to controls. Spearman correlation analysis between IGFs and HPV status showed significant correlations. Conclusions: We demonstrated elevated circulating levels and tissue expression of IGF-I and IGF-II in advancer cancer cervix patients, as compared with controls, with a converse trend being apparent for IGFBP-III. In future, associations of the IGF system and clinical outcome of cervical cancer patients in post treatment samples might point to significance in disease mapping as a prognostic marker after validation with a larger patient series.

Keywords

Insulin growth factors;insulin growth factor binding protein;cervical cancer;human papilloma virus

References

  1. Serrano ML, Sanchez-Gomez M, Bravo MM (2007). Insulin-like growth factor system gene expression in cervical scrapes from women with squamous intraepithelial lesions and cervical cancer. Growth Horm IGF Res, 17, 492-9. https://doi.org/10.1016/j.ghir.2007.07.001
  2. Sharma A, Rajappa M, Satyam A, Sharma M (2009). Cytokines (TH1 and TH2) in patients with advanced cervical cancer undergoing neoadjuvant chemoradiation: correlation with treatment response. Int J Gynecol Cancer, 19, 1269-75. https://doi.org/10.1111/IGC.0b013e3181a8efcc
  3. Sharma A, Rajappa M, Satyam A, Sharma M (2010). Oxidant/ anti-oxidant dynamics in patients with advanced cervical cancer: correlation with treatment response. Mol Cell Biochem, 341, 65-72. https://doi.org/10.1007/s11010-010-0437-2
  4. Sharma A, Rajappa M, Saxena A, Sharma M (2007). Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix. Int J Gynecol Cancer, 17, 879-85. https://doi.org/10.1111/j.1525-1438.2007.00883.x
  5. Sharma A, Rajappa M, Saxena A, Sharma M (2007). Telomerase activity as a tumor marker in Indian women with cervical intraepithelial neoplasia and cervical cancer. Mol Diagn Ther, 11, 193-201. https://doi.org/10.1007/BF03256241
  6. Shen MR, Hsu YM, Hsu KF, et al (2006). Insulin-like growth factor-1 is a potent stimulator of cervical cancer cell invasiveness and proliferation that is modulated by avh3 integrin signaling. Carcinogenesis, 27, 962-1. https://doi.org/10.1093/carcin/bgi336
  7. Wolk A, Mantzoros CS, Andersson SO, et al (1998). Insulin likegrowth factor 1 and prostate cancer risk: a population-based, case-control study. J Natl Cancer Inst (Bethesda), 90, 911-5. https://doi.org/10.1093/jnci/90.12.911
  8. Wu X, Tortolero-Luna G, Zhao H, et al (2003). Serum levels of insulin-like growth factor I and risk of squamous intraepithelial lesions of the cervix. Clin Cancer Res, 9, 3356-1.
  9. Wu X, Yu H, Amos CI, Hong WK, Spitz MR (2000). Joint effect of insulin-like growth factors and mutagen sensitivity in lung cancer risk. J Natl Cancer Inst (Bethesda), 92, 737-3. https://doi.org/10.1093/jnci/92.9.737
  10. Y-F Huang, M-R Shen, K-F Hsu, Y-M Cheng, C-Y Chou (2008). Clinical implications of insulin-like growth factor 1 system in early-stage cervical cancer. Bri J Cancer, 99, 1096-102. https://doi.org/10.1038/sj.bjc.6604661
  11. Yu H, Rohan T (2000). Role of insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst, 92, 1472-89. https://doi.org/10.1093/jnci/92.18.1472
  12. Zumkeller W (2001). IGFs and IGFBPs: surrogate markers for diagnosis and surveillance of tumor growth? Mol Pathol, 54, 285-8. https://doi.org/10.1136/mp.54.5.285
  13. Zur Hausen H (2002). Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer, 2, 342-50. https://doi.org/10.1038/nrc798
  14. Hankinson SE, Willett WC, Colditz GA, et al (1998). Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet, 351, 1393-6. https://doi.org/10.1016/S0140-6736(97)10384-1
  15. Harris TG, Burk RD, Yu H, et al (2008). Insulin-like growth factor axis and oncogenic human papillomavirus natural history. Cancer Epidemiol Biomarkers Prev, 17, 245-8. https://doi.org/10.1158/1055-9965.EPI-07-0686
  16. Jozefiak A, Pacholska-bogalska J, Myga-nowak M, et al (2008). Serum and tissue levels of insulin-like growth factor-I in women with dysplasia and HPV-positive cervical cancer. Molecular Medicine Reports, 1, 231-7.
  17. Kaaks R, Toniolo P, Akhmedkhanov A, et al (2000). Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst (Bethesda), 92, 1592-0. https://doi.org/10.1093/jnci/92.19.1592
  18. Koutsky L (2009). The epidemiology behind the HPV vaccine discovery. Ann Epidemiol, 19, 239-4. https://doi.org/10.1016/j.annepidem.2009.01.023
  19. Lee SW, Lee SY, Lee SR, Ju W, Kim SC (2010). Plasma levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in women with cervical neoplasia. J Gynecol Oncol, 21, 174-0. https://doi.org/10.3802/jgo.2010.21.3.174
  20. Lelbach A, Muzes G, Feher J (2005). The insulin-like growth factor system: IGFs, IGF-binding proteins and IGFBPproteases. Acta Physiol Hung, 92, 97-7. https://doi.org/10.1556/APhysiol.92.2005.2.1
  21. LeRoith D, Roberts CT Jr (2003). The insulin-like growth factor system and cancer. Cancer Lett, 195, 127-7. https://doi.org/10.1016/S0304-3835(03)00159-9
  22. Mathur SP, Mathur RS, Underwood PB, Kohler MF, Creasman WT (2003). Circulating levels of insulin-like growth factor-II and IGF-binding protein 3 in cervical cancer. Gynecol Oncol, 91, 486-3. https://doi.org/10.1016/j.ygyno.2003.08.023
  23. Mathur SP, Mathur RS, Young RC (2000). Cervical epidermal growth factor-receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer. Am J Reprod Immunol, 44, 222-30. https://doi.org/10.1111/j.8755-8920.2000.440406.x
  24. Munoz N, Castellsague X, de Gonzalez AB, Gissmann L (2006). Insulin Growth Factors and Binding Protein in Cervical Cancer Chapter 1: HPV in the etiology of human cancer. Vaccine, 24, 1-10. https://doi.org/10.1016/j.vaccine.2005.07.047
  25. Pollak M (2008). Insulin and insulin-like growth factor signaling in neoplasia. Nat Rev Cancer, 8, 915-8. https://doi.org/10.1038/nrc2536
  26. Renehan AG, Zwahlen M, Minder C, et al (2004). Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet, 363, 1346-3. https://doi.org/10.1016/S0140-6736(04)16044-3
  27. Schaffer A, Koushik A, Trottier H, et al (2007). Biomarkers of cervical cancer risk study team. Insulin-like growth factor-I and risk of high-grade cervical intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev, 16, 716-2. https://doi.org/10.1158/1055-9965.EPI-06-0924
  28. Serrano ML, Romero A, Cendales R, Sanchez-Gomez M, Bravo MM (2006). Serum levels of insulin-like growth factor-I and -II and insulin-like growth factor binding protein 3 in women with squamous intraepithelial lesions and cervical cancer. Biomedica, 26, 258-68. https://doi.org/10.7705/biomedica.v26i2.1415
  29. Ali O, Cohen P, Lee KW (2003). Epidemiology and biology of insulin-like growth factor binding protein-3 (IGFBP-III) as an anti-cancer molecule. Horm Metab Res, 35, 726-3. https://doi.org/10.1055/s-2004-814146
  30. Baserga R, Peruzzi F, Reiss K (2003). The IGF-I receptor in cancer biology. Int J Cancer, 107, 873-7. https://doi.org/10.1002/ijc.11487
  31. Boom R, Sol CJA, Salimans MMM, et al (1990). Rapid and simple detection method for purification of nucleic acids. J Clin Microbiol, 28, 495-3.
  32. Chen JC, Shao ZM, Sheikh MS, et al (1994). Insulin-like growth factor-binding protein enhancement of insulin-like growth factor-I (IGF-I)-mediated DNA synthesis and IGF-I binding in a human breast carcinoma cell line. J Cell Physiol, 158, 69-8. https://doi.org/10.1002/jcp.1041580110
  33. Collett-Solberg PF, Cohen P (2000). Genetics, chemistry, and function of the IGF/IGFBP system. Endocrine, 12, 121-6. https://doi.org/10.1385/ENDO:12:2:121
  34. De Mellow JS, Baxter RC (1998). Growth hormone-dependent insulin-like growth factor (IGF) binding protein both inhibits and potentiates IGF-I stimulated DNA synthesis in human skin fibroblasts. Biochem Biophys Res Commun, 156, 199-4.
  35. Dupont J, Pierre A, Froment P, Moreau C (2003). The insulin-like growth factor axis in cell cycle progression. Horm Metab Res, 35, 740-0. https://doi.org/10.1055/s-2004-814162
  36. Goswami B, Rajappa M, Sharma M, Sharma A (2008). Inflammation: its role and interplay in the development of cancer, with special focus on gynecological malignancies. Int J Gynecol Cancer, 18, 591-9. https://doi.org/10.1111/j.1525-1438.2007.01089.x
  37. Grimberg A, Cohen P (2000). Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol, 183, 1-9. https://doi.org/10.1002/(SICI)1097-4652(200004)183:1<1::AID-JCP1>3.0.CO;2-J
  38. Grimberg A (2003). Mechanisms by which IGF-I may promote cancer. Cancer Biol Ther, 2, 630-5.

Cited by

  1. Role of Cytokines in Genesis, Progression and Prognosis of Cervical Cancer vol.15, pp.9, 2014, https://doi.org/10.7314/APJCP.2014.15.9.3851
  2. IGF axis and other factors in HPV-related and HPV-unrelated carcinogenesis (Review) vol.32, pp.6, 2014, https://doi.org/10.3892/or.2014.3505
  3. IGF-1 from Adipose-Derived Mesenchymal Stem Cells Promotes Radioresistance of Breast Cancer Cells vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10115