MLM3 and MLM5 head and neck cancer models promote age-dependent musculoskeletal deterioration in mice

Head and Neck Cancer (HNC) patients are at high risk of developing cancer cachexia. While studies have focused on muscle, little is known regarding the consequences of non-bone metastatic HNC on the skeleton. Moreover, animal models used to date have only been evaluated in young, growing mice and not in fully developed adult animals. Therefore, this study focused on the effects of two murine HNC models, MLM3 and MLM5, on both muscle and bone in 2 and 12-month-old male mice. In young, but not adult mice, both tumors reduced growth as shown by shorter tibiae and altered growth plate size together with an increased bone remodeling. Tumor size was greater in the young compared to the adult mice, even though MLM3 tumors had comparable musculoskeletal effects in both ages. In both HNC models, muscle loss was accompanied by a corresponding loss in bone. The more cachectic MLM3 models induced severe bone deterioration at both microarchitecture and cellular levels. HNC had distinct growth inhibitory effects on the musculoskeletal system in young compared to adult mice. These observations encourage the use of mature, fully developed mice that better reflect the age of human HNC patients.