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Interlekina 6 en el cáncer de mama: Desde el metabolismo hacia el perfil genético
Resumen
Se ha reportado sobre la sobreexpresión de la citocina proinflamatoria IL-6 en el cáncer de mama. Apuntar. Investigar el papel de la IL-6 en el metabolismo y el cáncer de mama utilizando bases de datos públicas. Analizamos estos datos para la función biológica de IL-6, expresión, mutación somática y correlación en cáncer normal y de mama utilizando habilidades bioinformáticas. Dentro de la base de datos de Oncomine, la IL-6 representó una expresión reducida y no mostró diferencias significativas en la expresión entre el cáncer de mama y los controles normales. Las frecuencias de regulación positiva del ARNm de IL-6 en pacientes con carcinoma lobulillar invasivo de mama fueron mayores (5,41%) que en el carcinoma de mama invasivo (1,82%). Nuestros resultados revelaron que en 1.084 pacientes con cáncer de mama en cBioPortal, las frecuencias de alteración del gen IL-6 mostraron que la IL6 exhibió una frecuencia de alteración más baja (1,1%) y la amplificación del gen representó la mayoría de los cambios. La tasa de mutaciones puntuales en IL6 en cáncer de mama fue de 0,42 en la base de datos COSMIC. En conclusión, el ARNm observado y la tasa de mutación de IL6 pueden correlacionarse con la carga tumoral, controlando la metástasis del cáncer de mama y el metabolismo alterado.
Recibido: 22 de Octubre de 2023.
Aceptado: 13 de Enero de 2024.
Publicado online: 13 de Febrero de 2024.
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Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68: 7-30. [PubMed] [Google Scholar]
Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363: 1938-48. [PubMed] [Google Scholar]
Pooja S, Chaudhary P, Nayak LV, Rajender S, Saini KS, Deol D, Kumar S, Bid HK, Konwar R. Polymorphic variations in IL-1β, IL-6 and IL-10 genes, their circulating serum levels and breast cancer risk in Indian women. Cytokine. 2012;60: 122-8. [PubMed] [Google Scholar]
Fontanini G, Campani D, Roncella M, Cecchetti D, Calvo S, Toniolo A, Basolo F. Expression of interleukin 6 (IL-6) correlates with oestrogen receptor in human breast carcinoma. Br J Cancer. 1999;80(3-4):579-84. [PubMed] [Google Scholar]
Browning L, Patel MR, Horvath EB, Tawara K, Jorcyk CL. IL-6 and ovarian cancer: inflammatory cytokines in promotion of metastasis. Cancer Manag Res. 2018;10: 6685-93. [PubMed] [Google Scholar]
Schett G. Physiological effects of modulating the interleukin-6 axis. Rheumatology (Oxford). 2018;57(suppl_2):ii43-ii50. [PubMed] [Google Scholar]
Kishimoto T. The biology of interleukin-6. Blood. 1989;74:1-10. [PubMed] [Google Scholar]
Coulie PG, Vanhecke A, Van Damme J, Cayphas S, Poupart P, De Wit L, Content J. High-affinity binding sites for human 26-kDa protein (interleukin 6, B cell stimulatory factor-2, human hybridoma plasmacytoma growth factor, interferon-beta 2), different from those of type I interferon (alpha, beta), on lymphoblastoid cells. Eur J Immunol. 1987;17: 1435-40. [PubMed] [Google Scholar]
Hefler LA, Grimm C, Lantzsch T, Lampe D, Leodolter S, Koelbl H, Heinze G, Reinthaller A, Tong-Cacsire D, Tempfer C, Zeillinger R.. Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women. Clin Cancer Res. 2005;11: 5718-21. [PubMed] [Google Scholar]
Bachelot T, Ray-Coquard I, Menetrier-Caux C, Rastkha M, Duc A, Blay JY. Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. Br J Cancer. 2003;88: 1721-6. [PubMed] [Google Scholar]
Walter M, Liang S, Ghosh S, Hornsby PJ, Li R. Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene. 2009; 28: 2745-55. [PubMed] [Google Scholar]
Conze D, Weiss L, Regen PS, Bhushan A, Weaver D, Johnson P, Rincón M. Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells. Cancer Res. 2001;61: 8851-8. [PubMed] [Google Scholar]
Sasser AK, Sullivan NJ, Studebaker AW, Hendey LF, Axel AE, Hall BM. Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer. FASEB J. 2007;21: 3763-70. [PubMed] [Google Scholar]
Berishaj M, Gao SP, Ahmed S, Leslie K, Al-Ahmadie H, Gerald WL, Bornmann W, Bromberg JF. Stat3 is tyrosine
-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer. Breast Cancer Res. 2007;9: R32. [PubMed] [Google Scholar]
Sullivan NJ, Sasser AK, Axel AE, Vesuna F, Raman V, Ramirez N, Oberyszyn TM, Hall BM. Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene. 2009; 28: 2940-7. [PubMed] [Google Scholar]
Ravishankaran P, Karunanithi R. Clinical significance of preoperative serum interleukin-6 and C-reactive protein level in breast cancer patients. World J Surg Oncol. 2011;9: 18. [PubMed] [Google Scholar]
Nariţa D, Seclaman E, Ursoniu S, Ilina R, Cireap N, Anghel A. Expression of CCL18 and interleukin-6 in the plasma of breast cancer patients as compared with benign tumor patients and healthy controls. Rom J Morphol Embryol. 2011; 52: 1261-7. [PubMed] [Google Scholar]
Masjedi A, Hashemi V, Hojjat-Farsangi M, Ghalamfarsa G, Azizi G, Yousefi M, Jadidi-Niaragh F. The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer. Biomed Pharmacother. 2018; 108:1415-24 [PubMed] [Google Scholar]
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013; 6 (269):pl1. [PubMed] [Google Scholar]
Karlsson M, Zhang C, Méar L, Zhong W, Digre A, Katona B, Sjöstedt E, Butler L, Odeberg J, Dusart P, Edfors F, Oksvold P, von Feilitzen K, Zwahlen M, Arif M, Altay O, Li X, Ozcan M, Mardinoglu A, Fagerberg L, Mulder J, Luo Y, Ponten F, Uhlén M, Lindskog C. A single-cell type transcriptomics map of human tissues. Sci Adv. 2021;7: eabh2169. [PubMed] [Google Scholar]
Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs BB, Barrette TR, Anstet MJ, Kincead-Beal C, Kulkarni P, Varambally S, Ghosh D, Chinnaiyan AM. Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 2007;9: 166-80. [PubMed] [Google Scholar]
Forbes SA, Beare D, Gunasekaran P, et al. COSMIC: exploring the world's knowledge of somatic mutations in human cancer. Nucleic Acids Res. 2015;43(Database issue): D805-D811. [PubMed] [Google Scholar]
Vasaikar SV, Straub P, Wang J, Zhang B. LinkedOmics: analyzing multiomics data within and across 32 cancer types. Nucleic Acids Res. 2018;46: D956-d963. [PubMed] [Google Scholar]
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, Mering CV. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019; 47(D1):D607-D13. [PubMed] [Google Scholar]
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profling and interactive analyses. Nucleic Acids Res. 2017;45:W98-w102. [PubMed] [Google Scholar]
Mauer J, Denson JL, Brüning JC. Versatile functions for IL-6 in metabolism and cancer. Trends Immunol. 2015;36: 92-101. [PubMed] [Google Scholar]
Fu G, Song XC, Yang X, Peng T, Wang Y, Zhou GW. Protein subcellular localization profiling of breast cancer cells by dissociable antibody microarray staining. Proteomics. 2010;10: 1536-44. [PubMed] [Google Scholar]
Verboogen DRJ, Ter Beest M, Honigmann A, van den Bogaart G.. Secretory vesicles of immune cells contain only a limited number of interleukin 6 molecules. FEBS Lett. 2018; 592: 1535-44. [PubMed] [Google Scholar]
Mesquida M, Leszczynska A, Llorenç V, Adán A. Interleukin-6 blockade in ocular inflammatory diseases. Clin
Exp Immunol. 2014;176: 301-9. [PubMed] [Google Scholar]
Sansone P, Ceccarelli C, Berishaj M, et al. Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer. Nat Commun. 2016;7: 10442. [PubMed] [Google Scholar]
Gopinathan G, Milagre C, Pearce OM, et al. Interleukin-6 Stimulates Defective Angiogenesis. Cancer Res. 2015;75: 3098-107. [PubMed] [Google Scholar]
Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, Bloushtain-Qimron N, Kim JJ, Choudhury SA, Maruyama R, Wu Z, Gönen M, Mulvey LA, Bessarabova MO, Huh SJ, Silver SJ, Kim SY, Park SY, Lee HE, Anderson KS, Richardson AL, Nikolskaya T, Nikolsky Y, Liu XS, Root DE, Hahn WC, Frank DA, Polyak K. The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24⁻ stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011;121: 2723-35. [PubMed] [Google Scholar]
Porta C, De Amici M, Quaglini S, Paglino C, Tagliani F, Boncimino A, Moratti R, Corazza GR. Circulating interleukin-6 as a tumor marker for hepatocellular carcinoma. Ann Oncol. 2008;19: 353-8. [PubMed] [Google Scholar]
Turano M, Cammarota F, Duraturo F, Izzo P, De Rosa M. A Potential Role of IL-6/IL-6R in the Development and Management of Colon Cancer. Membranes (Basel). 2021;11: 312. [PubMed] [Google Scholar]
Ikeguchi M, Hatada T, Yamamoto M, Miyake T, Matsunaga T, Fukumoto Y, Yamada Y, Fukuda K, Saito H, Tatebe S. Serum interleukin-6 and -10 levels in patients with gastric cancer. Gastric Cancer. 2009;12: 95-100. [PubMed]
Kang S, Tanaka T, Inoue H, Ono C, Hashimoto S, Kioi Y, Matsumoto H, Matsuura H, Matsubara T, Shimizu K, Ogura H, Matsuura Y, Kishimoto T. IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome. Proc Natl Acad Sci U S A. 2020; 117: 22351-6. [PubMed] [Google Scholar]
Basolo F, Calvo S, Fiore L, Conaldi PG, Falcone V, Toniolo A. Growth-stimulating activity of interleukin 6 on human mammary epithelial cells
transfected with the int-2 gene. Cancer Res. 1993; 53: 2957-60. [PubMed] [Google Scholar]
Fontanini G, Campani D, Roncella M, Cecchetti D, Calvo S, Toniolo A, Basolo F.. Expression of interleukin 6 (IL-6) correlates with oestrogen receptor in human breast carcinoma. Br J Cancer. 1999; 80 (3-4): 579-584. [PubMed] [Google Scholar]
Dutkowska A, Szmyd B, Kaszkowiak M, Domańska-Senderowska D, Pastuszak-Lewandoska D, Brzeziańska-Lasota E, Kordiak J, Antczak A. Expression of inflammatory interleukins and selected miRNAs in non-small cell lung cancer. Sci Rep. 2021; 11: 5092. [PubMed] [Google Scholar]
Niu G, Wright KL, Huang M, Song L, Haura E, Turkson J, Zhang S, Wang T, Sinibaldi D, Coppola D, Heller R, Ellis LM, Karras J, Bromberg J, Pardoll D, Jove R, Yu H. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene. 2002; 21: 2000-8. [PubMed] [Google Scholar]
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