Muscle inflammation is regulated by NF-κB from multiple cells to control distinct states of wasting in cancer cachexia

• DOI: 10.1016/j.celrep.2024.114925
• Publication Date: 2024-10-31T07:53:28Z
• Authors: Benjamin R. Pryce; Alexander Oles; Erin E. Talbert; Martin J. Romeo; Silvia Vaena; Sudarshana Sharma; Victoria Spadafora; Lauren Tolliver; David A. Mahvi; Katherine A. Morgan; William P. Lancaster; Eryn Beal; Natlie Koren; Bailey Watts; Morgan Overstreet; Stefano Berto; Suganya Subramanian; Kubra Calisir; Anna Crawford; Brian Neelon; Michael C. Ostrowski; Teresa A. Zimmers; James G. Tidball; David J. Wang; Denis C. Guttridge
• Keywords: Cancer Cachexia

Although cancer cachexia is classically characterized as a systemic inflammatory disorder, emerging evidence indicates that weight loss also associates with local tissue inflammation. We queried the regulation of this inflammation and its causality to by exploring skeletal muscle, whose atrophy strongly poor outcomes. Using multiple mouse models patient samples, we show cachectic muscle marked enhanced innate immunity. Nuclear factor κB (NF-κB) activity in cells, including satellite myofibers, fibro-adipogenic progenitors, promotes macrophage expansion equally derived from infiltrating monocytes resident cells. Moreover, NF-κB-activated cells macrophages undergo crosstalk; NF-κB