Insulin-like growth factor-1 receptor expression in oral squamous cell carcinoma

Year 2011, , 354 - 361, 01.12.2011

Boby K. Joseph Devipriyaa B. Sundaram

https://doi.org/10.5799/ahinjs.01.2011.04.0071

Cited By: 2

Abstract

Objectives: The Insulin-like growth factor-I receptor (IGF-1R) plays critical roles in cancer development, proliferation, motility and survival. IGF-1R over expression is frequently found in various tumours and is often associated with an aggressive phenotype. Hence, the aim of the present study was to examine the expression of IGF-1R in normal oral mucosa, fibroepithelial polyps, dysplastic oral mucosa and well-differentiated squamous cell carcinomas. Materials and methods: A 3-layered streptavidin peroxidase immunohistochemical method was used to detect the expression of IGF-1R in normal oral mucosa, fibroepithelial polyps, dysplastic oral mucosa and well-differentiated squamous cell carcinomas. Results: All squamous cell carcinomas (15 out of 15 patients) showed intense immunoreactivity for IGF-1R. Moderate immunoreactivity was seen in dysplastic oral lesions (12 out of 12 lesions) with positive staining in the prickle cell layer. The staining distribution in the benign lesions (14 out of 14 lesions) was weaker and similar to that seen in normal oral mucosa (10 out of 10 samples) when compared to squamous cell carcinomas and dysplastic lesions. Conclusions: Our results demonstrate increased IGF-1 receptor expression in oral squamous cell carcinomas which suggests that IGF-1 may have an important role in the development of oral cancer. J Clin Exp Invest 2011; 2 (4): 354-361

Keywords

Growth factors, insulin-like growth factor receptor, epithelial dysplasia, Oral squamous cell carcinoma, immunohistochemistry

Insulin-like growth factor-1 receptor expression in oral squamous cell carcinoma

Abstract

Amaç: İnsülin benzeri büyüme faktörü-1 reseptörü (IGF-1R)\'ün kanser gelişiminde, proliferasyon ve sağkalımda önemli rolleri vardır. IGF-1R aşırı salınımı sıklıkla çeşitli tümörlerde gözlenir ve çoğunlukla agresif fenotiple birliktedir. Bu çalışmanın amacı normal ağız içi mukozası, fibroepitelyal polipler, displastik ağız mukozası ve iyi diferensiye yassı epitel hücreli karsinom\'da IGF-1R ekspresyonunu araştırmaktır. Gereç ve yöntem: IGF-1R ekspresyonunu normal ağız içi mukozası, fibroepitelyal polipler, displastik ağız mukozası ve iyi diferensiye yassı epitel hücreli karsinom\'da araştırmak için üç basamaklı bir streptavidin peroksidaz immunohistokimyasal yöntem kullanıldı. Bulgular: Yassı epitel hücreli karsinomların tümü (15 hasta) IGF-1R için yoğun immunoreaktivite gösterdi. Orta düzeyde immun reaktivite “prickle” hücre lezyonu tabakasıyla birlikte displastik ağız içi lezyonlarda (12 hastadan 12\'sinde) görüldü. Selim lezyonlarda (14 hasta) boyama dağılımı daha zayıftı ve yassı epitel hücreli karsinom ve displastik lezyonlarla kıyaslandığında, normal ağız mukozasında (10 örnek) görülene benzer şekilde idi. Sonuç: Bulgularımız, ağız içi yassı epitel hücreli karsinom ve oral kanser gelişiminde önemli rolleri olabileceğini telkin eder tarzda, IGF-1R\'nin ekspresyonunun arttığını göstermektedir.

Keywords

Büyüme faktörleri, insülin-benzer büyüme reseptörü, epitelyal displazi, ağız içi yassı epitel hücreli karsinom, immunohistokimya

References

• Barnes CJ, Ohshiro K, Rayala SK, El-Naggar AK, Ku- mar R. Insulin-like growth factor receptor as a thera- peutic target in head and neck cancer. Clin Cancer Res 2007; 13(15): 4291-99.
• Werner H, Katz J. The emerging role of the insulin- like growth factors in oral biology. J Dent Res 2004; 83(11): 832-36.
• Le Roith D, Werner H, Beitner-Johnson D, Roberts CT Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 1995; 16(2):143- 63.
• Valentinis B, Baserga R. IGF-1 receptor signaling in transformation and differentiation. Mol Pathol 2001; 54(3): 133-7.
• Ullrich A, Schlessinger J. Signal transduction by re- ceptors with tyrosine kinase activity. Cell 1990; 61(2): 203-12.
• Baserga R, Peruzzi F, Reiss K. The IGF-1 receptor in cancer biology. Int J Cancer 2003; 107(6): 873-877.
• Le Roith D, Roberts CT Jr. The insulin-like growth fac- tor system and cancer. Cancer Lett 2003; 195(2):127– 37.
• Werner H, Maor S. The insulin-like growth factor- 1 re- ceptor gene: a downstream target for oncogene and tumour suppressor action. Trends Endocrinol Metabol 2006; 17(6): 236-42.
• Samani AA, Yakar S, Le Roith D, Brodt P. The role of the IGF system in cancer growth and metasta- sis: overview and recent insights. Endocr Rev 2007; 28(1): 20-47.
• Pollak M. Insulin-like growth factor physiology and cancer risk. Eur J Cancer 2000; 36(10): 1224-28.
• Larsson O, Girnita A, Girnita L. Role of Insulin-like growth factor -1 receptor signaling in cancer. Br J Cancer 2005; 92(12): 2097-01.
• Pollak MN, Schernhammer ES, Hankinson SE. Insu- lin-like growth factors and neoplasia. Nat Rev Cancer 2004; 4(7): 505-18.
• Werner H, Bruchim I. The insulin-like growth factor-1 receptor as an oncogene. Arch Physiol Biochem 2009; 115(2): 58-71.
• Hellawell GO, Turner GD, Davies DR, Poulsom R, Brewster SF, Macaulay VM. Expression of the type 1 Insulin-like growth factor receptor is upregulated in primary prostate cancer and commonly persists in metastatic disease. Cancer Res 2002; 62(10): 2942- 50.
• Hakam A, Yeatman TJ, Lu L et al. Expression of in- sulin-like growth factor receptor-1 receptor in human colorectal cancer. Hum Pathol 1999; 30(10):1128-33.
• Kanter-Lewensohn L, Dricu A, Girnita L, Wejde J, Lar- sson O. Expression of insulin-like growth factor-1 re- ceptor (IGF-1R) and p27Kip1 in melanocytic tumors: a potential regulatory role of IGF-1 pathway in distri- bution of p27Kip1 between different cyclins. Growth Factors 2000; 17(3):193-202.
• Baker J, Liu JP, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1993; 75(1): 73-82.
• Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor-1 and type 1 IGF receptor. Cell 1993; 75(1): 59-72.
• Sell C, Dumenil G, Deveaud C. Effect of a null muta- tion of the type 1 IGF receptor gene on growth and transformation of mouse embryo fibroblasts. Mol CeII Biol 1994; 14(6): 3604-12.
• Coppola D, Ferber A, Miura M, et al. A functional in- sulin-like growth factor 1 receptor is required for the mitogenic and transforming activities of the epider- mal growth factor receptor. Mol Cell Biol 1994; 14(7): 4588-95.
• De Angelis T, Ferber A, Baserga R. Insulin-like growth factor 1 receptor is required for the mitogenic and transforming activities of the platelet-derived growth factor receptor. J Cell Physiol 1995; 164(1): 214-21.
• Sell C, Rubini M, Rubin R, Liu JP, Efstratiadis A, Baserga R. Simian virus 40 large tumor antigen is un- able to transform mouse embryonic fibroblasts lacking type-1 IGF receptor. Proc Natl Acad Sci USA 1993; 90(23): 11217-221.
• Baserga R, Sell C, Porcu P, Rubini M. The role of the IGF-I receptor in the growth and transformation of mammalian cells. Cell Prolif 1994; 27(2): 63-71.
• Kaleko M, Rutter WJ, Miller AD. Overexpression of the human insulin-like growth factor 1 receptor promotes ligand-dependent neoplastic transformation. Mol Cell Biol 1990; 10(2): 464-73.
• Werner H, Le Roith D. The role of the insulin-like growth factor system in human cancer. Adv Cancer Res 1996; 68(2): 183-223.
• Villa P, Kauffmann SH, Earnshaw WC. Caspases and caspase inhibitors. Trends Biochem Sci 1997; 22(10): 388-93.
• Wang L, Ma W, Markovich R, Lee WL, Wang PH. Insulin-like growth factor 1 modulates induction of apoptotic signaling in H9C2 cardiac muscle cells. En- docrinology 1998; 139(3): 1354-60.
• Resnicoff M, Coppola D, Sell C. Growth inhibition of human melanoma cells in nude mice by antisense strategies to the type I insulin-like growth factor recep- tor. Cancer Res 1994; 54(18): 4848-50.
• Werner H, Shalita-Chesner M, Abramovitch S, Idel- man G, Shaharabani-Gargir L, Glaser T. Regulation of the insulin-like growth factor-I receptor gene by on- cogenes and antioncogenes: Implications in human cancer. Mol Genet Metab 2000; 71(1-2): 315-320.
• Mitsiades CS, Mitsiades NS, McMullan CJ, et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell 2004; 5(3): 221–30.
• Arteaga CL, Osborne CK. Growth inhibition of human breast cancer cells in vitro with an antibody against the type 1 somatomedin receptor. Cancer Res1989; 49(22): 6237-41.
• Arteaga CL, Kitten LJ, Coronado EB, et al. Blockade of the type 1 somatomedin receptor inhibits growth in human breast cancer cells in athymic mice. J Clin In- vest 1989; 84(5): 1418-23.
• Gansler T, Furlanetto R, Gramling TS, et al. Antibody to type-1 insulin-like growth factor receptor inhibits growth of Wilm’s tumour in culture and in athymic mice. Am J Pathol 1989; 135(6): 961-66.
• Neuenschwander S, Schwartz A, Wood TL, Roberts CT Jr, Henninghausen L, Le Roith D. Involution of the lactating mammary gland is inhibited by the IGF sys- tem in a transgenic mouse model. J Clin Invest 1996; 97(10): 2225-32.
• Shapiro DN, Jones BG, Shapiro LH, Dias P, Hough- ton PJ. Antisense-mediated reduction in insulin-like growth factor-1 receptor expression suppresses the malignant phenotype of a human alveolar rhabdomy- osarcoma. J Clin Invest 1994; 94(3): 1235-42.
• Prager D. Li HL, Asa S, Melmed S. Dominant negative inhibition of tumorigenesis in vivo by human insulin- like growth factor 1 receptor mutant. Proc Natl Acad Sci 1994; 91(6): 2181-85.
• Amanso O, Iseki S. Expression, localization and development regulation of insulin-like growth factor 1 mRNA in rat submandibular gland. Arch Oral Biol 1993; 38(8): 671-7.
• Joseph BK, Savage NW, Daley TJ, Young WG. In situ hybridization evidence for a paracrine/autocrine role for insulin-like growth factor-1 in tooth development. Growth factors1996; 13(1-2): 11-7.
• Brady G, Crean SJ, Lorenzon A, Kapas S. IGF-1 protects human oral buccal mucosal epithelial cells from sodium nitroprusside-induced apoptosis via PI3- kinase. Growth Horm IGF Res 2008; 18(4): 298-306.
• Bhatavdekar JM, Patel DD, Vora HH, Balar DB. Circu- lating markers and growth factors as prognosticators in men with advanced tongue cancer. Tumour Biol 1993; 14(1): 55-8.
• Brady G, O’Regan E, Miller I, Ogungbowale A, Kapas S, Crean SJ. Serum levels of insulin like growth factors (IGFs) and their binding proteins (IGFBP’s)-1,-2,-3, in oral cancer. Int J Maxillofac Surg 2007; 36(3):259-62.
• Papadimitrakopoulou VA, Brown EN, Liu DD, et al. The prognostic role of loss of insulin-like growth fac- tor-binding protein-3 expression in head and neck car- cinogenesis. Cancer Lett 2006; 239(1): 136-143.
• Brady G, Crean SJ, Naik P, Kapas S. Upregulation of IGF-2 and IGF-1 receptor expression in oral cancer cell lines. Int J Oncol 2007; 31(4): 875-81.
• Wu X, Zhao H, Do KA, Johnson MM, Dong Q, Hong WK, Spitz MR. Serum levels of insulin growth factor (IGF-I) and IGF-binding protein predict risk of second primary tumors in patients with head and neck cancer. Clin Cancer Res 2004; 10(12): 3988-95.
• Slomiany MG, Black LA, Kibbey MM, Tingler MA, Day TA, Rosenzweig SA. Insulin-like growth factor-1 recep- tor and ligand targeting in head and neck squamous cell carcinoma. Cancer Lett 22007; 48(2): 269-279.
• Reszec J, Duraj E, Koda M, Musitowicz B, Sulkowska M. Insulin-like growth factor-1 receptor in human oral cancer. Rocz Akad Med Bialymst 2004; 49(Suppl 1): 58-60.
• Freier S, Weiss O, Eran M, Flyvbjerg A, Dahan R, Nephesh I, Safara T, Shiloni E, Raz I. Expression of the insulin-like growth factors and their receptors in ad- enocarcinoma of the colon. Gut 1999; 44(5): 704-8.
• Weber MM, Fottner C, Liu SB, Jung MC, Engelhardt D, Baretton GB. Overexpression of the insulin-like growth factor I receptor in human colon carcinomas. Cancer 2002; 95(10): 2086-95.