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GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy.
Ancey, Pierre-Benoit; Contat, Caroline; Boivin, Gael; Sabatino, Silvia; Pascual, Justine; Zangger, Nadine; Perentes, Jean Yannis; Peters, Solange; Abel, E Dale; Kirsch, David G; Rathmell, Jeffrey C; Vozenin, Marie-Catherine; Meylan, Etienne.
Afiliação
  • Ancey PB; Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Contat C; Swiss Cancer Center Léman, Lausanne, Switzerland.
  • Boivin G; Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Sabatino S; Swiss Cancer Center Léman, Lausanne, Switzerland.
  • Pascual J; Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Zangger N; Swiss Cancer Center Léman, Lausanne, Switzerland.
  • Perentes JY; Laboratory of Radiation Oncology, Department of Radiation Oncology, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Peters S; Department of Oncology, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Abel ED; Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Kirsch DG; Swiss Cancer Center Léman, Lausanne, Switzerland.
  • Rathmell JC; Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Vozenin MC; Swiss Cancer Center Léman, Lausanne, Switzerland.
  • Meylan E; Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Cancer Res ; 81(9): 2345-2357, 2021 05 01.
Article em En | MEDLINE | ID: mdl-33753374
Neutrophils are the most abundant circulating leucocytes and are essential for innate immunity. In cancer, pro- or antitumor properties have been attributed to tumor-associated neutrophils (TAN). Here, focusing on TAN accumulation within lung tumors, we identify GLUT1 as an essential glucose transporter for their tumor supportive behavior. Compared with normal neutrophils, GLUT1 and glucose metabolism increased in TANs from a mouse model of lung adenocarcinoma. To elucidate the impact of glucose uptake on TANs, we used a strategy with two recombinases, dissociating tumor initiation from neutrophil-specific Glut1 deletion. Loss of GLUT1 accelerated neutrophil turnover in tumors and reduced a subset of TANs expressing SiglecF. In the absence of GLUT1 expression by TANs, tumor growth was diminished and the efficacy of radiotherapy was augmented. Our results demonstrate the importance of GLUT1 in TANs, which may affect their pro- versus antitumor behavior. These results also suggest targeting metabolic vulnerabilities to favor antitumor neutrophils. SIGNIFICANCE: Lung tumor support and radiotherapy resistance depend on GLUT1-mediated glucose uptake in tumor-associated neutrophils, indicating that metabolic vulnerabilities should be considered to target both tumor cells as well as innate immune cells. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/9/2345/F1.large.jpg.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Falha de Tratamento / Proliferação de Células / Transportador de Glucose Tipo 1 / Adenocarcinoma de Pulmão / Neoplasias Pulmonares / Neutrófilos Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Falha de Tratamento / Proliferação de Células / Transportador de Glucose Tipo 1 / Adenocarcinoma de Pulmão / Neoplasias Pulmonares / Neutrófilos Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article