A Clue to Why Cancer Often Involves Muscle LossMany cancer patients gradually lose significant skele

A Clue to Why Cancer Often Involves Muscle LossMany cancer patients gradually lose significant skeletal muscle, both in mass and density. The condition is known as cachexia and it’s a bigger problem than just consequential fatigue or poorer functional performance. The amount of muscle loss impacts cancer survival, in part because it can lower patient tolerance to adverse effects resulting from chemotherapy and other treatments.In a new study using mouse models, published online in the April 25, 2022 issue of Nature Cell Biology, researchers at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences describe the mechanism they believe connects cancer to muscle loss. It involves extracellular vesicles (EV) – hollow spheres that carry proteins, lipids and genetic material between cells as a form of intercellular communication. “These are little sacs released by cancer cells into the bloodstream,” said co-corresponding study author Shizhen (Emily) Wang, PhD, professor of pathology. “These sacs can influence many tissues in the body, including muscle.” The study found that EVs released by cancer cells block a certain type of glycosylation (a type of protein modification) in muscles. This causes an abnormal increase in a calcium-release channel that quickly begins to break down muscle proteins. (Muscle function was studied in the lab of Simon Schenk, PhD, professor of orthopaedic surgery, UC San Diego School of Medicine, and co-corresponding author with Wang and first author Wei Yan, PhD, a postdoctoral fellow in Wang’s lab.)For many years, Wang and colleagues had observed that those mice with tumors were weaker, and sometimes smaller, than their cancer-free littermates.  “At first, we thought, ‘Oh well, I’m not surprised and the reviewers won’t be impressed,’ ” Wang said. “However, when Simon’s group performed a muscle mechanics assessment and found a difference between two groups he was blinded to, we knew there was a real mechanism to pursue.”The researchers began their work in 2016. They began with breast cancer mouse models, but believe a one-size-fits-all mechanism explaining muscle loss in all human cancers is unlikely. However, Wang said, “similar concepts may apply to other cancers.”Wang said she hopes their findings might eventually lead to a drug that blocks the identified pathway and prevents or slows cancer-related muscle loss. (Compounds that enhance the same glycosylation have been developed and are being tested in clinical trials for Alzheimer’s disease.)— Corey Levitan -- source link

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