MHC class I-related chain A and B ligands are differentially expressed in human cervical cancer cell lines

Cancer Cell International

Luis F Jave-Suarez⁴  Adrian Daneri-Navarro³  Alejandro Bravo-Cuellar⁴  Georgina Hernandez-Flores⁴  Pablo Ortiz-Lazareno⁴  Alicia del Toro-Arreola³  Oscar Gonzalez-Ramella³  Patricio Barros-Nuñez¹  Jesse Haramati⁴  Miriam Jimenez-Perez³  Angel Cid-Arregui²  Adriana Aguilar-Lemarroy⁴  Naela Arreygue-Garcia⁴  Susana del Toro-Arreola³ 

[1] División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México;Translational Immunology Unit, German Cancer Research Center (DKFZ) Im Neuenheimer Feld 280 69120-Heidelberg, Germany;Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México;División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México

关键词: Cervical cancer;    MICB;    MICA;   

Others  :  795537
DOI  :  10.1186/1475-2867-11-15

 received in 2010-12-02, accepted in 2011-06-01,  发布年份 2011

【 摘 要 】

Background

Natural killer (NK) cells are an important resource of the innate immune system directly involved in the spontaneous recognition and lysis of virus-infected and tumor cells. An exquisite balance of inhibitory and activating receptors tightly controls the NK cell activity. At present, one of the best-characterized activating receptors is NKG2D, which promotes the NK-mediated lysis of target cells by binding to a family of cell surface ligands encoded by the MHC class I chain-related (MIC) genes, among others. The goal of this study was to describe the expression pattern of MICA and MICB at the molecular and cellular levels in human cervical cancer cell lines infected or not with human papillomavirus, as well as in a non-tumorigenic keratinocyte cell line.

Results

Here we show that MICA and MICB exhibit differential expression patterns among HPV-infected (SiHa and HeLa) and non-infected cell lines (C33-A, a tumor cell line, and HaCaT, an immortalized keratinocyte cell line). Cell surface expression of MICA was higher than cell surface expression of MICB in the HPV-positive cell lines; in contrast, HPV-negative cells expressed lower levels of MICA. Interestingly, the MICA levels observed in C33-A cells were overcome by significantly higher MICB expression. Also, all cell lines released higher amounts of soluble MICB than of soluble MICA into the cell culture supernatant, although this was most pronounced in C33-A cells. Additionally, Real-Time PCR analysis demonstrated that MICA was strongly upregulated after genotoxic stress.

Conclusions

This study provides evidence that even when MICA and MICB share a high degree of homology at both genomic and protein levels, differential regulation of their expression and cell surface appearance might be occurring in cervical cancer-derived cells.

【 授权许可】

   
2011 del Toro-Arreola et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Trinchieri G: Biology of natural killer cells. Adv Immunol 1989, 47:187-376.
• [2]Natarajan K, Dimasi N, Wang J, Mariuzza RA, Margulies DH: Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination. Annu Rev Immunol 2002, 20:853-885.
• [3]Moretta L, Bottino C, Pende D, Castriconi R, Mingari MC, Moretta A: Surface NK receptors and their ligands on tumor cells. Semin Immunol 2006, 18:151-158.
• [4]Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T: Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 1999, 285:727-729.
• [5]Rincon-Orozco B, Kunzmann V, Wrobel P, Kabelitz D, Steinle A, Herrmann T: Activation of V gamma 9V delta 2 T cells by NKG2D. J Immunol 2005, 175:2144-2151.
• [6]Groh V, Bruhl A, El-Gabalawy H, Nelson JL, Spies T: Stimulation of T cell autoreactivity by anomalous expression of NKG2D and its MIC ligands in rheumatoid arthritis. Proc Natl Acad Sci USA 2003, 100:9452-9457.
• [7]Radosavljevic M, Bahram S: In vivo immunogenetics: from MIC to RAET1 loci. Immunogenetics 2003, 55:1-9.
• [8]Bahram S, Inoko H, Shiina T, Radosavljevic M: MIC and other NKG2D ligands: from none to too many. Curr Opin Immunol 2005, 17:505-509.
• [9]Cosman D, Mullberg J, Sutherland CL, Chin W, Armitage R, Fanslow W, Kubin M, Chalupny NJ: ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 2001, 14:123-133.
• [10]Sutherland CL, Chalupny NJ, Schooley K, VandenBos T, Kubin M, Cosman D: UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells. J Immunol 2002, 168:671-679.
• [11]Sutherland CL, Rabinovich B, Chalupny NJ, Brawand P, Miller R, Cosman D: ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with enhancement by IL-15. Blood 2006, 108:1313-1319.
• [12]Bahram S, Bresnahan M, Geraghty DE, Spies T: A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci USA 1994, 91:6259-6263.
• [13]Groh V, Bahram S, Bauer S, Herman A, Beauchamp M, Spies T: Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci USA 1996, 93:12445-12450.
• [14]Cerwenka A: New twist on the regulation of NKG2D ligand expression. J Exp Med 2009, 206:265-268.
• [15]Vetter CS, Groh V, thor Straten P, Spies T, Brocker EB, Becker JC: Expression of stress-induced MHC class I related chain molecules on human melanoma. J Invest Dermatol 2002, 118:600-605.
• [16]Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T: Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci USA 1999, 96:6879-6884.
• [17]Jinushi M, Takehara T, Tatsumi T, Kanto T, Groh V, Spies T, Kimura R, Miyagi T, Mochizuki K, Sasaki Y, Hayashi N: Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid. Int J Cancer 2003, 104:354-361.
• [18]Watson NF, Spendlove I, Madjd Z, McGilvray R, Green AR, Ellis IO, Scholefield JH, Durrant LG: Expression of the stress-related MHC class I chain-related protein MICA is an indicator of good prognosis in colorectal cancer patients. Int J Cancer 2006, 118:1445-1452.
• [19]Salih HR, Antropius H, Gieseke F, Lutz SZ, Kanz L, Rammensee HG, Steinle A: Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood 2003, 102:1389-1396.
• [20]Dulphy N, Berrou J, Campillo JA, Bagot M, Bensussan A, Toubert A: NKG2D Ligands Expression and NKG2D-Mediated NK Activity in Sezary Patients. J Invest Dermatol 2008.
• [21]Gasser S, Orsulic S, Brown EJ, Raulet DH: The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 2005, 436:1186-1190.
• [22]Tang KF, He CX, Zeng GL, Wu J, Song GB, Shi YS, Zhang WG, Huang AL, Steinle A, Ren H: Induction of MHC class I-related chain B (MICB) by 5-aza-2'-deoxycytidine. Biochem Biophys Res Commun 2008, 370:578-583.
• [23]Wu ZH, Shi Y, Tibbetts RS, Miyamoto S: Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli. Science 2006, 311:1141-1146.
• [24]Molinero LL, Fuertes MB, Girart MV, Fainboim L, Rabinovich GA, Costas MA, Zwirner NW: NF-kappa B regulates expression of the MHC class I-related chain A gene in activated T lymphocytes. J Immunol 2004, 173:5583-5590.
• [25]Venkataraman GM, Suciu D, Groh V, Boss JM, Spies T: Promoter region architecture and transcriptional regulation of the genes for the MHC class I-related chain A and B ligands of NKG2D. J Immunol 2007, 178:961-969.
• [26]Boyle P: Global burden of cancer. Lancet 1997, 349(Suppl 2):SII23-26.
• [27]Sankaranarayanan R, Ferlay J: Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol 2006, 20:207-225.
• [28]zur Hausen H: Papillomavirus infections--a major cause of human cancers. Biochim Biophys Acta 1996, 1288:F55-78.
• [29]Munoz N: Human papillomavirus and cancer: the epidemiological evidence. J Clin Virol 2000, 19:1-5.
• [30]Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV: The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 2002, 55:244-265.
• [31]Clifford GM, Smith JS, Plummer M, Munoz N, Franceschi S: Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 2003, 88:63-73.
• [32]Cogliano V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F: Carcinogenicity of human papillomaviruses. Lancet Oncol 2005, 6:204.
• [33]Burk RD, Chen Z, Van Doorslaer K: Human papillomaviruses: genetic basis of carcinogenicity. Public Health Genomics 2009, 12:281-290.
• [34]McMurray HR, Nguyen D, Westbrook TF, McAnce DJ: Biology of human papillomaviruses. Int J Exp Pathol 2001, 82:15-33.
• [35]Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE: Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 1988, 106:761-771.
• [36]Jordanova ES, Gorter A, Ayachi O, Prins F, Durrant LG, Kenter GG, van der Burg SH, Fleuren GJ: Human leukocyte antigen class I, MHC class I chain-related molecule A, and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients? Clin Cancer Res 2008, 14:2028-2035.
• [37]Azogui O, Avril MF, Margulis A, Guillard M, Caillou B, Prade M: Tumor-infiltrating CD3- NK cells are more effective than CD3+ T cells in killing autologous melanoma cells. J Invest Dermatol 1991, 97:425-429.
• [38]Waldhauer I, Steinle A: NK cells and cancer immunosurveillance. Oncogene 2008, 27:5932-5943.
• [39]Fujisaki H, Kakuda H, Shimasaki N, Imai C, Ma J, Lockey T, Eldridge P, Leung WH, Campana D: Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res 2009, 69:4010-4017.
• [40]Moretta L, Bottino C, Pende D, Castriconi R, Mingari MC, Moretta A: Surface NK receptors and their ligands on tumor cells. Semin Immunol 2006, 18:151-158.
• [41]Diefenbach A, Jensen ER, Jamieson AM, Raulet DH: Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 2001, 413:165-171.
• [42]Pende D, Rivera P, Marcenaro S, Chang CC, Biassoni R, Conte R, Kubin M, Cosman D, Ferrone S, Moretta L, Moretta A: Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Cancer Res 2002, 62:6178-6186.
• [43]Carbone E, Neri P, Mesuraca M, Fulciniti MT, Otsuki T, Pende D, Groh V, Spies T, Pollio G, Cosman D, Catalano L, Tassone P, Rotoli B, Venuta S: HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood 2005, 105:251-258.
• [44]Jinushi M, Takehara T, Tatsumi T, Hiramatsu N, Sakamori R, Yamaguchi S, Hayashi N: Impairment of natural killer cell and dendritic cell functions by the soluble form of MHC class I-related chain A in advanced human hepatocellular carcinomas. J Hepatol 2005, 43:1013-1020.
• [45]Holdenrieder S, Stieber P, Peterfi A, Nagel D, Steinle A, Salih HR: Soluble MICA in malignant diseases. Int J Cancer 2006, 118:684-687.
• [46]Salih HR, Goehlsdorf D, Steinle A: Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients. Hum Immunol 2006, 67:188-195.
• [47]Groh V, Wu J, Yee C, Spies T: Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 2002, 419:734-738.
• [48]Arreygue-Garcia NA, Daneri-Navarro A, del Toro-Arreola A, Cid-Arregui A, Gonzalez-Ramella O, Jave-Suarez LF, Aguilar-Lemarroy A, Troyo-Sanroman R, Bravo-Cuellar A, Delgado-Rizo V, Garcia-Iglesias T, Hernandez-Flores G, Del Toro-Arreola S: Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions. BMC Cancer 2008, 8:16. BioMed Central Full Text
• [49]de Sanjose S, Diaz M, Castellsague X, Clifford G, Bruni L, Munoz N, Bosch FX: Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis 2007, 7:453-459.
• [50]Textor S, Durst M, Jansen L, Accardi R, Tommasino M, Trunk MJ, Porgador A, Watzl C, Gissmann L, Cerwenka A: Activating NK cell receptor ligands are differentially expressed during progression to cervical cancer. Int J Cancer 2008, 123:2343-2353.
• [51]Oppenheim DE, Roberts SJ, Clarke SL, Filler R, Lewis JM, Tigelaar RE, Girardi M, Hayday AC: Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance. Nat Immunol 2005, 6:928-937.
• [52]Fernandez-Morera JL, Rodriguez-Rodero S, Lahoz C, Tunon A, Astudillo A, Garcia-Suarez O, Martinez-Borra J, Lopez-Vazquez A, Rodrigo L, Gonzalez S, Lopez-Larrea C: Soluble MHC class I chain-related protein B serum levels correlate with disease activity in relapsing-remitting multiple sclerosis. Hum Immunol 2008, 69:235-240.
• [53]Aguera-Gonzalez S, Boutet P, Reyburn HT, Vales-Gomez M: Brief residence at the plasma membrane of the MHC class I-related chain B is due to clathrin-mediated cholesterol-dependent endocytosis and shedding. J Immunol 2009, 182:4800-4808.
• [54]Rodriguez-Rodero S, Gonzalez S, Rodrigo L, Fernandez-Morera JL, Martinez-Borra J, Lopez-Vazquez A, Lopez-Larrea C: Transcriptional regulation of MICA and MICB: a novel polymorphism in MICB promoter alters transcriptional regulation by Sp1. Eur J Immunol 2007, 37:1938-1953.