Progression of Cancer Cachexia Alters Muscle Lactate Metabolism In ApcMin/+ Mice

Abstract

Roughly 100,000 individuals are diagnosed with colorectal cancer a year, 80% of these cases arise from adenomatous polyps. A mutation of the tumor suppressor gene, Adenomatous polyposis coli (Apc) results in multiple intestinal neoplasia (Min), thus the Apc (Min/+) mouse is a common colorectal cancer model. Cancer cells favor a highly glycolytic environment. As such, there is an induction of processes regulating lactate metabolism and lactate shuttling. How colorectal cancer influences skeletal muscle lactate metabolism is uncertain. Purpose: We investigated how muscle lactate metabolism is regulated during the progression of cancer cachexia in Apc (Min/+) mice. Methods: Male Min/+mice (n = 17) were classified by body mass loss: weight stable (WS, 蠄 5%, n = 5), and cachectic (CC, 6‐19%; n = 5). C57BL/6J (B6, n = 6) served as controls. Quadriceps muscle samples were extracted and real‐time PCR was conducted to quantify lactate‐related gene expression. Results: LDH‐A was reduced 47% in the CC mice compared to the WS mice (p < 0.05), while LDH‐B was not changed with cancer cachexia progression (p = 0.09). Monocarboxylate transporter 1 (MCT1) was induced 1.9‐fold in CC mice (p < 0.05) compared to the B6 mice. MCT4 was induced 1.7‐fold and 2.3‐fold in the CC mice compared to B6 and WS mice, respectively. Muscle CD147 was not changed with cancer cachexia progression (p = 0.31).ConclusionThe progression of cachexia in mice with colon cancer alters markers of lactate metabolism that may play a role in muscle wasting associated with cachexia.