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

2024; Cell Press; Volume: 43; Issue: 11 Linguagem: Inglês

10.1016/j.celrep.2024.114925

2639-1856

Benjamin R. Pryce, Alexander Oles, Erin E. Talbert, Martin J. Romeo, Silvia G. Vaena, Sudarshana M. Sharma, Victoria Spadafora, Lauren B. Tolliver, David A. Mahvi, Katherine A. Morgan, William P. Lancaster, Eliza W. Beal, Noam Koren, Bradley V. Watts, Morgan Overstreet, Stefano Berto, Suganya Subramanian, Kübra Çalışır, Anna Crawford, Brian Neelon, Michael C. Ostrowski, Teresa A. Zimmers, James G. Tidball, David J. Wang, Denis C. Guttridge,

Exercise and Physiological Responses

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 cachexia by exploring skeletal muscle, whose atrophy strongly associates with poor outcomes. Using multiple mouse models and patient samples, we show that cachectic muscle is marked by enhanced innate immunity. Nuclear factor κB (NF-κB) activity in multiple cells, including satellite cells, myofibers, and fibro-adipogenic progenitors, promotes macrophage expansion equally derived from infiltrating monocytes and resident cells. Moreover, NF-κB-activated cells and macrophages undergo crosstalk; NF-κB