Establishing That the VM‐M3 Model of Metastatic Cancer Exhibits Cancer Cachexia

While most cancer deaths are a result of metastatic disease, an estimated one‐third can be attributed to cachexia. Cancer cachexia is characterized by the loss of body weight and skeletal muscle mass, with or without fat loss, that cannot be fully reversed by conventional nutritional support and results in progressive functional impairment. There are many models of cancer cachexia, but none are ideal as they do not address all aspects of this multifaceted syndrome. Furthermore, there are no well characterized models of cancer cachexia associated with spontaneous systemic metastasis although cachexia occurs almost exclusively in patients with metastatic disease. The VM‐M3 model is a syngeneic mouse model derived from a spontaneous brain tumor (GBM) which, when implanted subcutaneously, results in rapid and systemic metastasis throughout the body, including to the liver, lungs, brain, kidneys, and spleen. As such, we sought to determine if cachexia occurs in the VM‐M3 model. Male and female VM/dk mice were randomly assigned to healthy (control) or diseased (VM‐M3 tumor‐bearing) groups. Diseased mice received a subcutaneous implantation of VM‐M3 cells while control animals received a sham injection of PBS. Diseased animals were euthanized at end of life along with an age, sex, and weight‐matched control mouse. Body weight, food intake, tumor growth, and blood glucose, ketones, and cytokine profile were measured weekly. Complete Blood Count was gathered immediately prior to end of life euthanasia. Gastrocnemius diameter and weight, and spleen and liver weight were measured at euthanasia. There was no difference in tumor growth rate or survival time between male and female diseased mice. Food intake and gastrocnemius weight and diameter were decreased in diseased mice of both sexes. Blood glucose, but not ketones, was lower in diseased mice of both sexes. Liver and spleen weights were increased in diseased mice of both sexes. Serum IL‐6 was elevated at 14 days and end‐of–life, while TNF‐α, G‐CSF, and CXCL1 were elevated at end‐of‐life, in diseased mice of both sexes. CXCL1 and CXCL10 were elevated in diseased males at 14 days. White blood cell and lymphocytes were higher, while platelet count and hematocrit were lower in diseased males. Monocytes were elevated in diseased females. Granulocytes were elevated while red blood cell count and hemoglobin were reduced in both diseased males and females. Support or Funding Information Scivation, Inc.