سامانه مدیریت نشریات علمی دانشگاه شاهد

Kheshtchin, Nasim, Arab, Samaneh, Hadjati, Jamshid. (1398). Blockade of Hypoxia: The Impact on Tumor Growth in an Experimental Tumor Model. , 2(1), 35-40. doi: 10.32598/Immunoregulation.1.3.153
Nasim Kheshtchin; Samaneh Arab; Jamshid Hadjati. "Blockade of Hypoxia: The Impact on Tumor Growth in an Experimental Tumor Model". , 2, 1, 1398, 35-40. doi: 10.32598/Immunoregulation.1.3.153
Kheshtchin, Nasim, Arab, Samaneh, Hadjati, Jamshid. (1398). 'Blockade of Hypoxia: The Impact on Tumor Growth in an Experimental Tumor Model', , 2(1), pp. 35-40. doi: 10.32598/Immunoregulation.1.3.153
Kheshtchin, Nasim, Arab, Samaneh, Hadjati, Jamshid. Blockade of Hypoxia: The Impact on Tumor Growth in an Experimental Tumor Model. , 1398; 2(1): 35-40. doi: 10.32598/Immunoregulation.1.3.153

Blockade of Hypoxia: The Impact on Tumor Growth in an Experimental Tumor Model

Immunoregulation
مقاله 5، دوره 2، شماره 1 - شماره پیاپی 3، مهر 2019، صفحه 35-40    اصل مقاله (921.27 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.32598/Immunoregulation.1.3.153
نویسندگان
Nasim Kheshtchin1؛ Samaneh Arab2؛ Jamshid Hadjati* 1
1Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
چکیده
Background: Tumor microenvironment is an active factor participating in immunoregulation, thereby preventing immunosurveillance and limiting the efficacy of anticancer therapies. Hypoxia as a major characteristic of solid tumors causes the expression of Hypoxia-Inducible Factor-1α (HIF-1α). This is a transcription factor that mediates hypoxic responses of tumor cells and involves in the expression of tumor immunosuppression-related genes.
Materials and Methods: In this study, we used a mouse 4T1 breast cancer model.
Results: Our obtained data revealed that in vivo administration of PX-478, an inhibitor of oxygen sensitive HIF-1α, reduced the expression of Forkhead box P3 (Foxp3) transcript, a molecule that is directly controlled by HIF-1. The level of vascular endothelial growth factor, another gene controlled by HIF-1, remained unchanged. The observed results were in correlation with delayed tumor growth in tumor-bearing mice.
Conclusion: Our findings indicate that the reduction in Foxp3 expression through HIF-1α inhibition using PX-478 may contribute to tumor regression.
کلیدواژه‌ها
Cancer؛ Hypoxia-Inducible Factor-1α (HIF-1α)؛ Hypoxia؛ PX-478؛ Foxp3؛ VEGF
مراجع

Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, Wang LP, et al. Tumor hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature. 2011; 475(7355):226-30. [DOI:10.1038/nature10169] [PMID]
Sitkovsky M, Lukashev D. Regulation of immune cells by local-tissue oxygen tension: HIF1α and adenosine receptors. Nature Reviews Immunology. 2005; 5(9):712-21. [DOI:10.1038/nri1685] [PMID]
Noman MZ, Benlalam H, Hasmim M, Chouaib S. Cytotoxic T cells-stroma interactions. Bull Cancer. 2011; 98(2):E19-24. [PMID]
Noman MZ, Janji B, Kaminska B, Van Moer K, Pierson S, Przanowski P, et al. Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression. Cancer Research. 2011; 71(18):5976-86. [DOI:10.1158/0008-5472.CAN-11-1094] [PMID]
Noman MZ, Messai Y, Carre T, Akalay I, Meron M, Janji B, et al. Microenvironmental hypoxia orchestrating the cell stroma cross talk, tumor progression and antitumor response. Critical Reviews™ in Immunology. 2011; 31(5):357-77. [DOI:10.1615/CritRevImmunol.v31.i5.10] [PMID]
Semenza GL. Targeting HIF-1 for cancer therapy. Nature Reviews Cancer. 2003; 3(10):721-32. [DOI:10.1038/nrc1187] [PMID]
Shi YH, Fang WG. Hypoxia-Inducible Factor-1 in tumor angiogenesis. World Journal of Gastroenterology. 2004; 10(8):1082-7. [DOI:10.3748/wjg.v10.i8.1082] [PMCID]
Semenza GL. Defining the role of Hypoxia-Inducible Factor 1 in cancer biology and therapeutics. Oncogene. 2010; 29(5):625-34. [DOI:10.1038/onc.2009.441] [PMID] [PMCID]
Kim JwG, Ping D, Chi V. Effects of hypoxia on tumor metabolism. Cancer and Metastasis Reviews. 2007; 26(2):291-8. [DOI:10.1007/s10555-007-9060-4] [PMID]
Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nature Reviews Cancer. 2011; 11(6):393-410. [DOI:10.1038/nrc3064] [PMID]
Koh MY, Spivak Kroizman T, Venturini S, Welsh S, Williams RR, Kirkpatrick DL, et al. Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the Hypoxia-Inducible Factor-1alpha. Molecular Cancer Therapeutics. 2008; 7(1):90-100. [DOI:10.1158/1535-7163.MCT-07-0463] [PMID]
Welsh S, Williams R, Kirkpatrick L, Paine Murrieta G, Powis G. Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of Hypoxia-Inducible Factor-1alpha. Molecular Cancer Therapeutics. 2004; 3(3):233-44. [PMID]
Clambey ET, McNamee EN, Westrich JA, Glover LE, Campbell EL, Jedlicka P. Hypoxia-Inducible Factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa. National Academy of Sciences of the United States of America. 2012; 109(41):E2784-93. [DOI:10.1073/pnas.1202366109] [PMID] [PMCID]
Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H. HIF1α–dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. Journal of Experimental Medicine. 2011; 208(7):1367-76. [DOI:10.1084/jem.20110278] [PMCID]
Vergis R, Corbishley CM, Norman AR, Bartlett J, Jhavar S, Borre M, et al. Intrinsic markers of tumor hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: A retrospective analysis of two randomised radiotherapy trials and one surgical cohort study. The Lancet Oncology. 2008; 9(4):342-51. [DOI:10.1016/S1470-2045(08)70076-7]
Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nature Reviews Cancer. 2008; 8(6):425-37. [DOI:10.1038/nrc2438] [PMCID]
Melillo G. Targeting hypoxia cell signaling for cancer therapy. Cancer and Metastasis Reviews. 2007; 26(2):341-52. [DOI:10.1007/s10555-007-9059-x]
Takenaga K. Angiogenic signaling aberrantly induced by tumor hypoxia. Frontiers in Bioscience. 2011; 16:31-48. [DOI:10.2741/3674]
Noman MZ, Buart S, Van Pelt J, Richon C, Hasmim M, Leleu N, et al. The cooperative induction of Hypoxia-Inducible Factor-1 alpha and STAT3 during hypoxia induced an impairment of tumor susceptibility to CTL-mediated cell lysis. The Journal of Immunology. 2009; 182(6):3510-21. [DOI:10.4049/jimmunol.0800854]
Eltzschig HK, Ibla JC, Furuta GT, Leonard MO, Jacobson KA, Enjyoji K, et al. Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: Role of ectonucleotidases and adenosine A2B receptors. The Journal of Experimental Medicine. 2003; 198(5):783-96. [DOI:10.1084/jem.20030891] [PMCID]
Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. The Journal of Experimental Medicine. 2007; 204(6):1257-65. [DOI:10.1084/jem.20062512] [PMCID]
Zarek P, Huang CT, Lutz ER, Kowalski J, Horton MR, Linden J, et al. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood. 2008; 111(1):251-9. [DOI:10.1182/blood-2007-03-081646] [PMCID]
Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, et al. PD-L1 is a novel direct target of HIF-1 , and its blockade under hypoxia enhanced MDSC-mediated T cell activation. The Journal of Experimental Medicine. 2014; 211(5):781-90. [DOI:10.1084/jem.20131916] [PMCID]
Doedens AL, Stockmann C, Rubinstein MP. Macrophage expression of Hypoxia-Inducible Factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Research. 2010; 70(19):7465-75. [DOI:10.1158/0008-5472.CAN-10-1439] [PMCID]
Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, et al. Control of TH17/treg balance by Hypoxia-Inducible Factor 1. Cell. 2011; 146(5):772-84. [DOI:10.1016/j.cell.2011.07.033] [PMCID]

آمار
تعداد مشاهده مقاله: 685
تعداد دریافت فایل اصل مقاله: 716