Intramuscular CMT-167 Tumors Produce a Mild Cachexia Phenotype in C57BL/6J Mice.

Background: Cancer cachexia is a debilitating syndrome characterized by irreversible losses in skeletal muscle mass, with or without losses in adipose tissue. Cancer cachexia is an underrecognized syndrome that impacts ~50% of all cancer patients and accounts for up to ~20% of all cancer deaths [1, 2]. Lung cancer remains one of the deadliest cancers in the United States with an estimated 137,000 deaths in the year 2021 alone [3]. Lung cancer is highly comorbid with cancer cachexia [4]. Pre-clinical models are heavily relied upon to study both lung cancer and cancer cachexia, however there is a need to develop novel models to study the relationship between the two diseases. We therefore characterized the cachexia phenotype in the CMT-167 syngeneic lung cancer model. Methods: Male C57BL6/J mice, aged 8-10 weeks, were administered an intramuscular (IM) injection of either 0.5x10 Results: Compared to tumor free (TF) mice, we observed lower terminal tumor-adjusted bodyweight, adipose tissue mass, gastrocnemius mass, quadriceps mass, and gastrocnemius myofiber CSA. CMT-167 tumor bearing (TB) mice did not lose bodyweight relative to starting weight, but instead failed to gain as much weight as TF controls. CMT-167 TB mice exhibited increased concentrations of circulating markers of cachexia and muscle wasting, such as IL-6 and TNF-α, although there was no difference in transcription of E3 ubiquitin ligases Conclusion: The IM CMT-167 model is a syngeneic lung cancer model of mild cachexia. CMT-167 TB mouse is a novel model in which to study cancer cachexia induction, skeletal muscle atrophy, and immune checkpoint inhibitor clearance mechanisms in the context of lung cancer.