Obesity-induced changes in cancer cells and their microenvironment : Mechanisms and therapeutic perspectives to manage dysregulated lipid metabolism
Lee-Rueckert, Miriam (Wihuri Research Institute)
Canyelles, Marina (Institut d'Investigació Biomèdica Sant Pau)
Tondo Colomer, Mireia (Institut d'Investigació Biomèdica Sant Pau)
Rotllan, Noemi (Institut d'Investigació Biomèdica Sant Pau)
Kovanen, Petri T. (Wihuri Research Institute)
Llorente-Cortés, Vicenta (Institut d'Investigació Biomèdica Sant Pau)
Escolà-Gil, Joan Carles (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	Obesity has been closely related to cancer progression, recurrence, metastasis, and treatment resistance. We aim to review recent progress in the knowledge on the obese macroenvironment and the generated adipose tumor microenvironment (TME) inducing lipid metabolic dysregulation and their influence on carcinogenic processes. Visceral white adipose tissue expansion during obesity exerts systemic or macroenvironmental effects on tumor initiation, growth, and invasion by promoting inflammation, hyperinsulinemia, growth-factor release, and dyslipidemia. The dynamic relationship between cancer and stromal cells of the obese adipose TME is critical for cancer cell survival and proliferation as well. Experimental evidence shows that secreted paracrine signals from cancer cells can induce lipolysis in cancer-associated adipocytes, causing them to release free fatty acids and acquire a fibroblast-like phenotype. Such adipocyte delipidation and phenotypic change is accompanied by an increased secretion of cytokines by cancer-associated adipocytes and tumor-associated macrophages in the TME. Mechanistically, the availability of adipose TME free fatty acids and tumorigenic cytokines concomitant with the activation of angiogenic processes creates an environment that favors a shift in the cancer cells toward an aggressive phenotype associated with increased invasiveness. We conclude that restoring the aberrant metabolic alterations in the host macroenvironment and in adipose TME of obese subjects would be a therapeutic option to prevent cancer development. Several dietary, lipid-based, and oral antidiabetic pharmacological therapies could potentially prevent tumorigenic processes associated with the dysregulated lipid metabolism closely linked to obesity.
Ajuts:	Instituto de Salud Carlos III PI19-00136 Instituto de Salud Carlos III PI21-00140
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article de revisió ; recerca ; Versió publicada
Matèria:	Adipocytes, cancer ; Cholesterol ; Fibroblasts, fatty acids ; Lipids ; Macrophages ; Obesity ; Tumor microenvironment
Publicat a:	Seminars in Cancer Biology, Vol. 93 (august 2023) , p. 36-51, ISSN 1096-3650

DOI: 10.1016/j.semcancer.2023.05.002
PMID: 37156344

16 p, 2.3 MB

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