Tumor-Induced Cholesterol Efflux from Macrophages Drives IL-4 Mediated Reprogramming and Tumor Progression

Goossens, Pieter; Rodríguez-Vita, Juan; Etzerodt, Anders; Massé, Marion; Rastoin, Olivia; Gouirand, Victoire; Eck, Miranda Van; Ulas, Thomas; Papantonopoulou, Olympia; Bébien, Magali; Turner, Martin; Manh, Thien Phong Vu; Dalod, Marc; Auphan-Anezin, Nathalie; Schultze, Joachim L.; Lawrence, Toby

doi:10.2139/ssrn.3283707

Cited by 3 publications

(1 citation statement)

References 66 publications

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“…and increases interleukin-4-mediated reprogramming. This series of events, explain how these macrophages are forced to adopt a tumor-promoting, immunosuppressive response rather than an intrinsic tumoricidal activity which would normally suppress tumor development (28).…”

Section: Contribution Of Cholesterol Synthesismentioning

confidence: 99%

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

Ouweneel

Thomas

Sorci‐Thomas

2020

Journal of Lipid Research

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Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.

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Section: Contribution Of Cholesterol Synthesismentioning

confidence: 99%

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

Ouweneel

Thomas

Sorci‐Thomas

2020

Journal of Lipid Research

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Tumor immune microenvironment modulation by cholesterol in hepatocellular carcinoma

et al. 2022

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Hepatocellular carcinoma (HCC) is considered one of the most aggressive tumors worldwide. The consumption of lipid-enriched diets, mainly high cholesterol, induces oxidative stress and chronic inflammation, leading to HCC progression. Moreover, fatty acids and cholesterol could display differential responses on immune cells inside the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs) represent one of the most critical leukocytes in the tumor microenvironment (TME) displaying pro-tumoral responses and one of the mainly cholesterol donors to cancer cells. Immunotherapy or cholesterol regulators, alone or combined, would represent an effective strategy for HCC treatment. Nonetheless, steatotic etiology from non-alcoholic fatty liver disease (NAFLD)-HCC tumors has been unexpectedly resulting in highly aggressive behavior.

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Role of cholesterol homeostasis in MASH-driven hepatocellular carcinoma: not just a neutral fat

Ribas

2024

Explor Dig Dis

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer and its death rate is rising faster than that of any other cancer, while we still lack effective treatments. The increasing incidence of liver cancer in western countries is closely associated with the growing prevalence of metabolic dysfunction-associated steatohepatitis (MASH) linked to metabolic diseases. While the contribution of lipids in the progression of MASH pathogenesis and its progression to HCC is well recognized, the specific contribution of cholesterol is subject to controversy. The liver plays a central role in cholesterol metabolism, where the majority of its biosynthesis, storage, excretion, recycling, and conversion into bile acids occur. Moreover, cholesterol is implicated in numerous hepatocyte cellular processes, encompassing endoplasmic reticulum function, formation of lipid microdomains in the plasma membrane, metabolism of lipoproteins, and mitochondrial function and performance. Therefore, it is not surprising that cholesterol plays key roles in initiation, promotion, and survival of HCC cells and there are several lines of evidence pointing to that cancer cells are subverting cholesterol metabolism to foster their proliferation and survival through various mechanisms. This narrative review provides a concise overview of the physiological and pathological roles of cholesterol in the transition from healthy hepatocytes to HCC, in the context of MASH. Gaining further understanding of how hepatic cancer cells disrupt cholesterol homeostasis and how these perturbations impact cancer progression will facilitate the identification of novel and more effective cancer treatment strategies in this complex and devastating disease.

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Tumor-Induced Cholesterol Efflux from Macrophages Drives IL-4 Mediated Reprogramming and Tumor Progression

Cited by 3 publications

References 66 publications

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

Tumor immune microenvironment modulation by cholesterol in hepatocellular carcinoma

Role of cholesterol homeostasis in MASH-driven hepatocellular carcinoma: not just a neutral fat

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