Glut1 expression in tumor-associated neutrophils promotes lung cancer growth and resistance to radiotherapy
| Autor: | Marie-Catherine Vozenin, Nadine Zangger, Caroline Contat, Jean Yannis Perentes, Justine Pascual, Gael Boivin, Silvia Sabatino, David G. Kirsch, Jeffrey C. Rathmell, Solange Peters, E. Dale Abel, Etienne Meylan, Pierre-Benoit Ancey |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research endocrine system Lung Neoplasms Cell Survival Neutrophils Glucose uptake Adenocarcinoma of Lung Tumor initiation Article 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor Tumor Microenvironment Medicine Animals Humans Treatment Failure Lung cancer skin and connective tissue diseases mouse Cell Proliferation Mice Knockout Glucose Transporter Type 1 Innate immune system biology integumentary system business.industry Glucose transporter Cancer hallmarks medicine.disease 3. Good health carbohydrates (lipids) Mice Inbred C57BL modulation Disease Models Animal 030104 developmental biology Oncology 030220 oncology & carcinogenesis Case-Control Studies Cancer research biology.protein Adenocarcinoma cells GLUT1 business human activities |
| Zdroj: | Cancer Res |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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