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Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis.
Li, Peishan; Lu, Ming; Shi, Jiayuan; Gong, Zheng; Hua, Li; Li, Qing; Lim, Bora; Zhang, Xiang H-F; Chen, Xiaowen; Li, Sheng; Shultz, Leonard D; Ren, Guangwen.
Afiliación
  • Li P; The Jackson Laboratory, Bar Harbor, ME, USA.
  • Lu M; Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Shi J; The Jackson Laboratory, Bar Harbor, ME, USA.
  • Gong Z; Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, Shanghai, China.
  • Hua L; The Jackson Laboratory, Bar Harbor, ME, USA.
  • Li Q; The Jackson Laboratory, Bar Harbor, ME, USA.
  • Lim B; The Jackson Laboratory, Bar Harbor, ME, USA.
  • Zhang XH; The Jackson Laboratory, Bar Harbor, ME, USA.
  • Chen X; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Li S; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
  • Shultz LD; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
  • Ren G; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Nat Immunol ; 21(11): 1444-1455, 2020 11.
Article en En | MEDLINE | ID: mdl-32958928
ABSTRACT
Acquisition of a lipid-laden phenotype by immune cells has been defined in infectious diseases and atherosclerosis but remains largely uncharacterized in cancer. Here, in breast cancer models, we found that neutrophils are induced to accumulate neutral lipids upon interaction with resident mesenchymal cells in the premetastatic lung. Lung mesenchymal cells elicit this process through repressing the adipose triglyceride lipase (ATGL) activity in neutrophils in prostaglandin E2-dependent and -independent manners. In vivo, neutrophil-specific deletion of genes encoding ATGL or ATGL inhibitory factors altered neutrophil lipid profiles and breast tumor lung metastasis in mice. Mechanistically, lipids stored in lung neutrophils are transported to metastatic tumor cells through a macropinocytosis-lysosome pathway, endowing tumor cells with augmented survival and proliferative capacities. Pharmacological inhibition of macropinocytosis significantly reduced metastatic colonization by breast tumor cells in vivo. Collectively, our work reveals that neutrophils serve as an energy reservoir to fuel breast cancer lung metastasis.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Metabolismo de los Lípidos / Células Madre Mesenquimatosas / Neoplasias Pulmonares / Neutrófilos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Metabolismo de los Lípidos / Células Madre Mesenquimatosas / Neoplasias Pulmonares / Neutrófilos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos