Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression

Dalton, Heather J. y Pradeep, Sunila y McGuire, Michael y Hailemichael, Yared y MA, Shaolin y Lyons, Yasmin y Armaiz Pena, Guillermo N. y Previs, Rebecca A. y Hansen, Jean Marie y Rupaimoole, Rajesha y González Villasana, Vianey y Cho, Min Soon y Wu, Sherry Y. y Mangala, Lingegowda S. y Jennings, Nicholas B. y Hu, Wei y Langley, Robert y Mu, Hong y Andreeff, Michael y Bar-Eli, Menashe y Overwijk, Willem y Ram, Prahlad y Lopez Berestein, Gabriel y Coleman, Robert L. y Sood, Anil K. (2017) Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression. Clinical Cancer Research, 23 (22). pp. 7034-7046. ISSN 1078-0432

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Abstract Purpose: VEGF-targeted therapies have modest efficacy in cancerpatients, butacquiredresistance iscommon. Themechanisms underlying such resistance are poorly understood. Experimental Design: To evaluate the potential role of immune cells in the development of resistance to VEGF blockade, we first established a preclinical model of adaptive resistance to anti-VEGF therapy. Additional in vitro and in vivo studies were carried out to characterize the role of macrophages in such resistance. Results: Using murine cancer models of adaptive resistance to anti-VEGF antibody (AVA), we found a previously unrecognized roleofmacrophagesinsuchresistance.Macrophageswereactively recruited to the tumor microenvironment and were responsible for the emergence of AVA resistance. Depletion of macrophages following emergence of resistance halted tumor growth and prolonged survival of tumor-bearing mice. In a macrophagedeficient mouse model, resistance to AVA failed to develop, but could be induced by injection of macrophages. Downregulation of macrophage VEGFR-1 and VEGFR-3 expression accompanied upregulation of alternative angiogenic pathways, facilitating escape from anti-VEGF therapy. Conclusions: These findings provide a new understanding of the mechanisms underlying the modest efficacy of current antiangiogenesis therapies and identify new opportunities for combinationapproachesforovarianandothercancers. ClinCancerRes; 23(22); 7034–46. �2017 AACR.

Tipo de elemento: Article
Divisiones: Medicina
Usuario depositante: Lic. Josimar Pulido
Creadores:
CreadorEmailORCID
Dalton, Heather J.NO ESPECIFICADONO ESPECIFICADO
Pradeep, SunilaNO ESPECIFICADONO ESPECIFICADO
McGuire, MichaelNO ESPECIFICADONO ESPECIFICADO
Hailemichael, YaredNO ESPECIFICADONO ESPECIFICADO
MA, ShaolinNO ESPECIFICADONO ESPECIFICADO
Lyons, YasminNO ESPECIFICADONO ESPECIFICADO
Armaiz Pena, Guillermo N.NO ESPECIFICADONO ESPECIFICADO
Previs, Rebecca A.NO ESPECIFICADONO ESPECIFICADO
Hansen, Jean MarieNO ESPECIFICADONO ESPECIFICADO
Rupaimoole, RajeshaNO ESPECIFICADONO ESPECIFICADO
González Villasana, VianeyNO ESPECIFICADONO ESPECIFICADO
Cho, Min SoonNO ESPECIFICADONO ESPECIFICADO
Wu, Sherry Y.NO ESPECIFICADONO ESPECIFICADO
Mangala, Lingegowda S.NO ESPECIFICADONO ESPECIFICADO
Jennings, Nicholas B.NO ESPECIFICADONO ESPECIFICADO
Hu, WeiNO ESPECIFICADONO ESPECIFICADO
Langley, RobertNO ESPECIFICADONO ESPECIFICADO
Mu, HongNO ESPECIFICADONO ESPECIFICADO
Andreeff, MichaelNO ESPECIFICADONO ESPECIFICADO
Bar-Eli, MenasheNO ESPECIFICADONO ESPECIFICADO
Overwijk, WillemNO ESPECIFICADONO ESPECIFICADO
Ram, PrahladNO ESPECIFICADONO ESPECIFICADO
Lopez Berestein, GabrielNO ESPECIFICADONO ESPECIFICADO
Coleman, Robert L.NO ESPECIFICADONO ESPECIFICADO
Sood, Anil K.NO ESPECIFICADONO ESPECIFICADO
Fecha del depósito: 30 Abr 2020 01:48
Última modificación: 14 Mayo 2020 18:55
URI: http://eprints.uanl.mx/id/eprint/17479

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