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The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
Published on: June 16, 2018
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Cholesterol efflux pathways hinder KRAS-driven lung tumor progenitor cell expansion
Emma Guilbaud1, Thibault Barouillet2, Marius Ilie3
1Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France; Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
Cell Stem Cell
|June 2, 2023
Summary
Targeting cholesterol efflux pathways can combat lung cancer. Disrupting these pathways in progenitor cells fuels tumor growth, but therapies like HDL or cholesterol removal show promise in preclinical models and human lung adenocarcinoma.
Area of Science:
- Oncology
- Metabolic pathways
- Cancer biology
Background:
- Cholesterol efflux pathways are critical in cellular lipid homeostasis.
- Dysregulation of these pathways is implicated in various diseases, including cancer.
- Cancer cells can hijack metabolic pathways to support their growth and survival.
Purpose of the Study:
- To investigate the role of cholesterol efflux pathways in lung cancer development and progression.
- To explore the therapeutic potential of targeting cholesterol efflux in lung cancer.
- To understand the mechanisms by which cholesterol efflux impacts the tumor microenvironment.
Main Methods:
- Utilized a KRASG12D mouse model of lung adenocarcinoma.
- Disrupted cholesterol efflux pathways in epithelial progenitor cells.
- Assessed tumor growth, transcriptional landscape, and tumor microenvironment.
- Investigated the effects of apolipoprotein A-I overexpression and cyclodextrin-mediated cholesterol removal.
- Analyzed human lung adenocarcinoma (LUAD) samples for cholesterol efflux pathway perturbations.
Main Results:
- Disruption of cholesterol efflux in epithelial progenitor cells promoted tumor growth and created a pro-tolerogenic tumor microenvironment (TME).
- Overexpression of apolipoprotein A-I (ApoA-I) and increased HDL levels protected against tumor development.
- HDL blunted a feedback loop between growth factor signaling and cholesterol efflux exploited by cancer cells.
- Cholesterol removal therapy with cyclodextrin reduced tumor burden by suppressing progenitor cell proliferation.
- Cholesterol efflux pathway alterations were observed in human LUAD.
Conclusions:
- Defective cholesterol efflux in progenitor cells drives lung cancer growth and progression.
- Cholesterol efflux pathways represent a vulnerable target for lung cancer therapy.
- Cholesterol removal therapy holds promise as a metabolic strategy for treating lung cancer, particularly targeting progenitor cells.
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