Cell reports · 2025
Early adipose tissue wasting in a preclinical model of human lung cancer cachexia.
СтатьяНазвание и аннотация: Перевод в очереди
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Snoke Deena B, van der Velden Jos L, Bellafleur Emma R, Dearborn Jacob S, Lenahan Sean M, Beal Alexandra E, Aboushousha Reem, Heininger Skyler C J, Ather Jennifer L, Mank Madeleine M, Sarausky Hailey, Stephenson Daniel, Reisz Julie A, D'Alessandro Angelo, Majumdar Devdoot, Ahern Thomas P, Xu Kaiwen, Sandler Kim L, Landman Bennett A, Janssen-Heininger Yvonne M W, Poynter Matthew E, Seward David J, Toth Michael J
Аннотация
Cancer cachexia (CC), a syndrome of skeletal muscle and adipose wasting, reduces responsiveness to therapies and increases mortality. There are no approved treatments for CC, which may relate to discordance between preclinical models and human CC. To address the need for clinically relevant models of lung CC, we generated inducible, lung epithelial cell-specific KrasG12D/+ (G12D) mice. G12D mice develop CC over a protracted time course and phenocopy tissue and tumor, cellular, mutational, transcriptomic, and metabolic characteristics of human lung CC. G12D mice demonstrate early loss of adipose, a phenotype that was apparent across numerous models of CC and translates to patients with lung cancer. Tumor-released factors promote adipocyte lipolysis, a driver of adipose wasting in CC, and adipose wasting was inversely related to tumor burden. Thus, G12D mice model key features of human lung CC and highlight a role for early tumor metabolic reprogramming of adipose tissue in CC.