proteína Alfa-1 antitripsina y su papel en la fisiopatología del cáncer
DOI:
https://doi.org/10.18633/biotecnia.v26.2287Palabras clave:
Antiproteasa, Progresión tumoral, Inflamación, Matriz extracelular, Respuesta inmuneResumen
La proteína α1-AT posee una amplia gama de funciones biológicas, su función principal es proteger al pulmón contra las elastasas producidas por los neutrófilos. Sin embargo, también está relacionada con diferentes procesos patológicos, como el cáncer. Entre los tipos de cáncer a los que se ha asociado se encuentra cáncer de mama, próstata, pulmón, cuello uterino, vejiga y colorrectal, entre otros. Asimismo, diferentes estudios han reportado concentraciones aumentadas en los pacientes con cáncer en comparación con sujetos control. Además, la proteína α1-AT se ha asociado como un posible biomarcador en diferentes tipos de cáncer y se ha relacionado con la progresión tumoral. Actualmente, los mecanismos fisiopatológicos y moleculares de la α1-AT en el cáncer aún no son claros. Sin embargo, podría estar participando en diferentes procesos biológicos y moleculares en el microambiente tumoral, lo que podría ser una causa del aumento de la concentración sistémica. En conclusión, el presente trabajo se enfoca en describir la estructura de la α1-AT y recopilar sus funciones más relevantes en procesos fisiológicos y patológicos, como el cáncer.
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Aldecoa, F. and Ávila, J. (2021). La vía canónica PI3K/AKT/mTOR y sus alteraciones en cáncer. Horizonte Médico (Lima), 21(4), p. e1547. Available at: https://doi.org/10.24265/horizmed.2021.v21n4.15. DOI: https://doi.org/10.24265/horizmed.2021.v21n4.15
Aquino, M.T.P. et al. (2016). Challenges and future perspectives of T cell immunotherapy in cancer. Immunology Letters, 166(2), pp. 117–133. Available at: https://doi.org/10.1016/j.imlet.2015.05.018. DOI: https://doi.org/10.1016/j.imlet.2015.05.018
Avalos, G. et al. (2019). Circulating soluble levels of MIF in women with breast cancer in the molecular subtypes : relationship with Th17 cytokine profile. Clinical and Experimental Medicine, pp. 3–9. Available at: https://doi.org/10.1007/s10238-019-00559-6. DOI: https://doi.org/10.1007/s10238-019-00559-6
Baker, S.K. and Strickland, S. (2020). A critical role for plasminogen in inflammation. Journal of Experimental Medicine, 217(4). Available at: https://doi.org/10.1084/jem.20191865. DOI: https://doi.org/10.1084/jem.20191865
Barzon, V. et al. (2022). Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency. International Journal of Molecular Sciences, 23(17). Available at: https://doi.org/10.3390/ijms23179859. DOI: https://doi.org/10.3390/ijms23179859
Bashir, A. et al. (2016). Novel variants of SERPIN1A gene: Interplay between alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease. Respiratory Medicine, 117, pp. 139–149. Available at: https://doi.org/10.1016/j.rmed.2016.06.005. DOI: https://doi.org/10.1016/j.rmed.2016.06.005
Bates, J.P. et al. (2018). Mechanisms of immune evasion in breast cancer. BMC Cancer, 18(1), p. 556. Available at: https://doi.org/10.1186/s12885-018-4441-3. DOI: https://doi.org/10.1186/s12885-018-4441-3
Belmonte I, Blanco I, Bustamante A, Cadenas S, Casas F, Curí S, Chiner E, Dasí F, Esquinas C, Escribano A, et al. (2016). No TitDéficit de alfa-1 antitripsina: fisiopatología, enfermedades relacionadas, diagnóstico y tratamientole. In Respira. 2da ed, pp. 41–58.
Bergin, D.A. et al. (2014). The Circulating Proteinase Inhibitor α-1 Antitrypsin Regulates Neutrophil Degranulation and Autoimmunity. Science Translational Medicine, 6(217). Available at: https://doi.org/10.1126/scitranslmed.3007116. DOI: https://doi.org/10.1126/scitranslmed.3007116
Blanchard, V. et al. (2011). N-glycosylation and biological activity of recombinant human alpha1-antitrypsin expressed in a novel human neuronal cell line. Biotechnology and Bioengineering, 108(9), pp. 2118–2128. Available at: https://doi.org/10.1002/bit.23158. DOI: https://doi.org/10.1002/bit.23158
Capoun, O. et al. (2015). Diagnostic Importance of Selected Protein Serum Markers in the Primary Diagnostics of Prostate Cancer. Urologia Internationalis, 95(4), pp. 429–435. Available at: https://doi.org/10.1159/000431364. DOI: https://doi.org/10.1159/000431364
Chang, Y.-H. et al. (2012). Secretomic Analysis Identifies Alpha-1 Antitrypsin (A1AT) as a Required Protein in Cancer Cell Migration, Invasion, and Pericellular Fibronectin Assembly for Facilitating Lung Colonization of Lung Adenocarcinoma Cells. Molecular & Cellular Proteomics, 11(11), pp. 1320–1339. Available at: https://doi.org/10.1074/mcp.M112.017384. DOI: https://doi.org/10.1074/mcp.M112.017384
Crisford, H., Sapey, E. and Stockley, R.A. (2018). Proteinase 3; a potential target in chronic obstructive pulmonary disease and other chronic inflammatory diseases. Respiratory Research, 19(1), p. 180. Available at: https://doi.org/10.1186/s12931-018-0883-z. DOI: https://doi.org/10.1186/s12931-018-0883-z
Draxler, D., Sashindranath, M. and Medcalf, R. (2016). Plasmin: A Modulator of Immune Function. Seminars in Thrombosis and Hemostasis, 43(02), pp. 143–153. Available at: https://doi.org/10.1055/s-0036-1586227. DOI: https://doi.org/10.1055/s-0036-1586227
Ehlers, M.R. (2014). Immune-modulating effects of alpha-1 antitrypsin. Biological Chemistry, 395(10), pp. 1187–1193. Available at: https://doi.org/10.1515/hsz-2014-0161. DOI: https://doi.org/10.1515/hsz-2014-0161
Enewold, L. et al. (2012). SERPINA1 and ELA2 polymorphisms are not associated with COPD or lung cancer. Anticancer Research, 32(9), pp. 3923–3928.
Ercetin et al. (2019). Clinical Significance of SERPINA1 Gene and Its Encoded Alpha1-antitrypsin Protein in NSCLC. Cancers, 11(9), p. 1306. Available at: https://doi.org/10.3390/cancers11091306.
Foil, K.E. (2021). Variants of SERPINA1 and the increasing complexity of testing for alpha-1 antitrypsin deficiency. Therapeutic Advances in Chronic Disease, 12_suppl, pp. 33–48. Available at: https://doi.org/10.1177/20406223211015954. DOI: https://doi.org/10.1177/20406223211015954
Geraghty, P. et al. (2014). α 1 -Antitrypsin Activates Protein Phosphatase 2A to Counter Lung Inflammatory Responses. American Journal of Respiratory and Critical Care Medicine, 190(11), pp. 1229–1242. Available at: https://doi.org/10.1164/rccm.201405-0872OC. DOI: https://doi.org/10.1164/rccm.201405-0872OC
Hanahan, D. (2022). Hallmarks of Cancer: New Dimensions. Cancer Discovery, 12(1), pp. 31–46. Available at: https://doi.org/10.1158/2159-8290.CD-21-1059. DOI: https://doi.org/10.1158/2159-8290.CD-21-1059
Hanahan, D. and Weinberg, R.A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), pp. 646–674. Available at: https://doi.org/10.1016/j.cell.2011.02.013. DOI: https://doi.org/10.1016/j.cell.2011.02.013
Hirasawa, Y. et al. (2021). Diagnostic performance of OncuriaTM, a urinalysis test for bladder cancer. Journal of Translational Medicine, 19(1), pp. 1–10. Available at: https://doi.org/10.1186/s12967-021-02796-4. DOI: https://doi.org/10.1186/s12967-021-02796-4
Jaberie, H., Hosseini, S.V. and Naghibalhossaini, F. (2020). Evaluation of Alpha 1-Antitrypsin for the Early Diagnosis of Colorectal Cancer. Pathology & Oncology Research, 26(2), pp. 1165–1173. Available at: https://doi.org/10.1007/s12253-019-00679-0. DOI: https://doi.org/10.1007/s12253-019-00679-0
Janciauskiene, S. et al. (2019). Clinical significance of serpina1 gene and its encoded alpha1-antitrypsin protein in nsclc. Cancers, 11(9). Available at: https://doi.org/10.3390/cancers11091306. DOI: https://doi.org/10.3390/cancers11091306
Janciauskiene, S. et al. (2021). Potential Roles of Acute Phase Proteins in Cancer: Why Do Cancer Cells Produce or Take Up Exogenous Acute Phase Protein Alpha1-Antitrypsin?. Frontiers in Oncology, pp. 1–10. Available at: https://doi.org/10.3389/fonc.2021.622076. DOI: https://doi.org/10.3389/fonc.2021.622076
Janciauskiene, S.M. et al. (2011). The discovery of α1-antitrypsin and its role in health and disease. Respiratory Medicine, 105(8), pp. 1129–1139. Available at: https://doi.org/10.1016/j.rmed.2011.02.002. DOI: https://doi.org/10.1016/j.rmed.2011.02.002
Keeratichamroen, S. et al. (2020). Identification of potential cervical cancer serum biomarkers in Thai patients. Oncology Letters, 19(6), pp. 3815–3826. Available at: https://doi.org/10.3892/ol.2020.11519. DOI: https://doi.org/10.3892/ol.2020.11519
Kim, Y. et al. (1999). Nitric Oxide Protects PC12 Cells from Serum Deprivation-Induced Apoptosis by cGMP-Dependent Inhibition of Caspase Signaling’. 19(16), pp. 6740–6747. DOI: https://doi.org/10.1523/JNEUROSCI.19-16-06740.1999
Kunder, M., Lakshmaiah, V. and Moideen Kutty, A. V. (2018). Plasma Neutrophil Elastase, α1-Antitrypsin, α2-Macroglobulin and Neutrophil Elastase–α1-Antitrypsin Complex Levels in patients with Dengue Fever. Indian Journal of Clinical Biochemistry, 33(2), pp. 218–221. Available at: https://doi.org/10.1007/s12291-017-0658-1. DOI: https://doi.org/10.1007/s12291-017-0658-1
Lechowicz, U. et al. (2020). Post-translational modifications of circulating alpha-1-antitrypsin protein. International Journal of Molecular Sciences, 21(23), pp. 1–18. Available at: https://doi.org/10.3390/ijms21239187. DOI: https://doi.org/10.3390/ijms21239187
Lim, J.-H. et al. (2020). Alpha-1 antitrypsin inhibits formaldehyde-induced apoptosis of human peritoneal mesothelial cells. Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, 40(2), pp. 124–131. Available at: https://doi.org/10.1177/0896860819887288. DOI: https://doi.org/10.1177/0896860819887288
Ljujic, M. et al. (2016). ALPHA-1 antitrypsin affects U0126-induced cytotoxicity in colon cancer cell line (HCT116). Molecular Biology, 50(1), pp. 153–156. Available at: https://doi.org/10.1134/S002689331601012X. DOI: https://doi.org/10.1134/S002689331601012X
López-Árias, E. et al. (2012). Alpha 1-antitrypsin: A novel tumor-associated antigen identified in patients with early-stage breast cancer. Electrophoresis, 33(14), pp. 2130–2137. Available at: https://doi.org/10.1002/elps.201100491. DOI: https://doi.org/10.1002/elps.201100491
Lorincz, R. and Curiel, D.T. (2020). Advances in alpha-1 antitrypsin gene therapy. American Journal of Respiratory Cell and Molecular Biology, 63(5), pp. 560–570. Available at: https://doi.org/10.1165/RCMB.2020-0159PS. DOI: https://doi.org/10.1165/rcmb.2020-0159PS
Manne, V. and Kowdley, K. V. (2020). Alpha1-Antitrypsin Deficiency: A Cause of Chronic Liver Disease. Clinics in Liver Disease, 24(3), pp. 483–492. Available at: https://doi.org/10.1016/j.cld.2020.04.010. DOI: https://doi.org/10.1016/j.cld.2020.04.010
Marando, M., Rayroux, C. and Bergeron, A. (2022). Alpha-1 antitrypsin deficiency. Revue Medicale Suisse, 18(804), pp. 2169–2174. Available at: https://doi.org/10.53738/REVMED.2022.18.804.2169. DOI: https://doi.org/10.53738/REVMED.2022.18.804.2169
Marijanovic, E.M. et al. (2019). Reactive centre loop dynamics and serpin specificity. Scientific Reports, 9(1), pp. 1–15. Available at: https://doi.org/10.1038/s41598-019-40432-w. DOI: https://doi.org/10.1038/s41598-019-40432-w
Miyake, M. et al. (2013). Investigation of CCL18 and A1AT as potential urinary biomarkers for bladder cancer detection. BMC Urology, 13(1), p. 1. Available at: https://doi.org/10.1186/1471-2490-13-42. DOI: https://doi.org/10.1186/1471-2490-13-42
Motawi, T. et al. (2016). Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection. Balkan Journal of Medical Genetics, 19(2), pp. 35–44. Available at: https://doi.org/10.1515/bjmg-2016-0034. DOI: https://doi.org/10.1515/bjmg-2016-0034
Ortega, V.E. et al. (2020). The Effects of Rare SERPINA1 Variants on Lung Function and Emphysema in SPIROMICS. American Journal of Respiratory and Critical Care Medicine, 201(5), pp. 540–554. Available at: https://doi.org/10.1164/rccm.201904-0769OC. DOI: https://doi.org/10.1164/rccm.201904-0769OC
Pérez-Holanda, S. et al. (2014). Serum concentration of alpha-1 antitrypsin is significantly higher in colorectal cancer patients than in healthy controls. BMC Cancer, 14(1), p. 355. Available at: https://doi.org/10.1186/1471-2407-14-355. DOI: https://doi.org/10.1186/1471-2407-14-355
Remih, K., Amzou, S. and Strnad, P. (2021). Alpha1-antitrypsin deficiency: New therapies on the horizon. Current Opinion in Pharmacology, 59, pp. 149–156. Available at: https://doi.org/10.1016/j.coph.2021.06.001. DOI: https://doi.org/10.1016/j.coph.2021.06.001
De Serres & Blanco (2014). Role of alpha-1 antitrypsin in human health and disease. Journal of Internal Medicine, 276(4), pp. 311–335. Available at: https://doi.org/10.1111/joim.12239. DOI: https://doi.org/10.1111/joim.12239
Shakya, R. et al. (2017). Mutant p53 upregulates alpha-1 antitrypsin expression and promotes invasion in lung cancer. Oncogene, 36(31), pp. 4469–4480. Available at: https://doi.org/10.1038/onc.2017.66. DOI: https://doi.org/10.1038/onc.2017.66
Stockley, R.A. (2015). α1-antitrypsin: A polyfunctional protein?. The Lancet Respiratory Medicine, 3(5), pp. 341–343. Available at: https://doi.org/10.1016/S2213-2600(15)00094-6. DOI: https://doi.org/10.1016/S2213-2600(15)00094-6
Strnad, P., McElvaney, N.G. and Lomas, D.A. (2020). Alpha 1 -Antitrypsin Deficiency. New England Journal of Medicine. Edited by D.L. Longo, 382(15), pp. 1443–1455. Available at: https://doi.org/10.1056/NEJMra1910234. DOI: https://doi.org/10.1056/NEJMra1910234
Sun, Z. and Yang, P. (2004). Role of imbalance between neutrophil elastase and α1-antitrypsin in cancer development and progression. Lancet Oncology, 5(3), pp. 182–190. Available at: https://doi.org/10.1016/S1470-2045(04)01414-7. DOI: https://doi.org/10.1016/S1470-2045(04)01414-7
Tan, S.G., Cunliffe, W.J. and Macgregor, A.J. (1976). Acne Mechanica. British Medical Journal, 1(6002), p. 130. Available at: https://doi.org/10.1136/bmj.1.6002.130. DOI: https://doi.org/10.1136/bmj.1.6002.130
Thun, G.A. et al. (2013). Causal and Synthetic Associations of Variants in the SERPINA Gene Cluster with Alpha1-antitrypsin Serum Levels. PLoS Genetics. Edited by G. Gibson, 9(8), p. e1003585. Available at: https://doi.org/10.1371/journal.pgen.1003585. DOI: https://doi.org/10.1371/journal.pgen.1003585
Timms, J.F. et al. (2014). Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies. Proteomics - Clinical Applications, 8(11–12), pp. 982–993. Available at: https://doi.org/10.1002/prca.201400063. DOI: https://doi.org/10.1002/prca.201400063
Tumpara, S. et al. (2020). The Delivery of α1-Antitrypsin Therapy Through Transepidermal Route: Worthwhile to Explore. Frontiers in Pharmacology, 11. Available at: https://doi.org/10.3389/fphar.2020.00983. DOI: https://doi.org/10.3389/fphar.2020.00983
Urquidi, V. et al. (2012). Diagnostic Potential of Urinary α1-Antitrypsin and Apolipoprotein E in the Detection of Bladder Cancer. Journal of Urology, 188(6), pp. 2377–2383. Available at: https://doi.org/10.1016/j.juro.2012.07.094. DOI: https://doi.org/10.1016/j.juro.2012.07.094
Verathamjamras, C. et al. (2023). Label-free quantitative proteomics reveals aberrant expression levels of LRG, C9, FN, A1AT and AGP1 in the plasma of patients with colorectal cancer. Clinical Proteomics, 20(1), pp. 1–16. Available at: https://doi.org/10.1186/s12014-023-09407-y. DOI: https://doi.org/10.1186/s12014-023-09407-y
Vianello, A. et al. (2021). Correlation between α1-antitrypsin deficiency and SARS-CoV-2 infection: Epidemiological data and pathogenetic hypotheses. Journal of Clinical Medicine, 10(19), pp. 1–12. Available at: https://doi.org/10.3390/jcm10194493. DOI: https://doi.org/10.3390/jcm10194493
Wang, M. et al. (2017). Mechanism of immune evasion in breast cancer. OncoTargets and Therapy, 10, pp. 1561–1573. Available at: https://doi.org/10.2147/OTT.S126424. DOI: https://doi.org/10.2147/OTT.S126424
Wu, D.M. et al. (2020). Alpha-1 antitrypsin induces epithelial-to-mesenchymal transition, endothelial-to-mesenchymal transition, and drug resistance in lung cancer cellS. OncoTargets and Therapy, 13, pp. 3751–3763. Available at: https://doi.org/10.2147/OTT.S242579. DOI: https://doi.org/10.2147/OTT.S242579
Yuan, Y. et al. (2018). Anti-inflammaging effects of human alpha-1 antitrypsin. Aging Cell, 17(1), pp. 1–11. Available at: https://doi.org/10.1111/acel.12694. DOI: https://doi.org/10.1111/acel.12694
Zhao, Z. et al. (2018). Silence of α1-antitrypsin inhibits migration and proliferation of triple negative breast cancer cells. Medical Science Monitor, 24, pp. 6851–6860. Available at: https://doi.org/10.12659/MSM.910665. DOI: https://doi.org/10.12659/MSM.910665
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