Progressive development of melanoma-induced cachexia differentially impacts organ systems in mice [GAS RNA-seq]

Cachexia is a systemic wasting syndrome that develops in many cancers and increases mortality. Despite its importance, it is largely unknown how cachexia progressively and differentially induces tissue wasting. Although cachexia occurs also in pediatric patients, little is known on the underlying mechanisms. Here, we have used pediatric melanoma xenografts to determine the progression and tissue-specific impact of juvenile cachexia on skeletal muscles, heart, white and brown adipose, liver, and brain. We find that the heart and muscles undergo wasting at early stages and are the tissues most strongly impacted transcriptionally. Beyond wasting, we identify general and organ-specific transcriptional changes that likely indicate derangement of organ/tissue function by cachexia. Moreover, also the transcriptome of tissues that do not undergo wasting, such as the brain, is profoundly remodeled by cachexia. Altogether, this study provides insight into the progression of melanoma-induced pediatric cachexia and its differential impact on distinct organ systems. Overall design: RNA-sequencing data from gastrocnemius skeletal muscle at different time points of cachexia progression. Female 2-month-old NCI Ath/nude mice were injected with cachectic melanoma cells (CAC), non-cachectic melanoma cells (NCAC), or mock injected (Con). The time points analyzed are 2, 4, 6, and 8 weeks (wk) post cancer cell injection.