Colorectal cancer (CRC) cachexia results in skeletal muscle dysfunction and significantly reduces survival. Multiple preclinical models have been developed to study the biological mechanisms of CRC cachexia, including the widely used mouse model of subcutaneous inoculation using colorectal carcinoma cells (C26). The CT26 cell line, another murine model used to study colorectal cancer, has been suggested to not induce as severe cachexia phenotype. However, to date no studies have directly compared the potential of C26 versus CT26 adenocarcinoma cells in causing CRC cachexia. Importantly, the possible differences in their biological mechanisms by which C26 and CT26 impact skeletal muscle function have also not been elucidated. Herein, we sought to characterize the potential effect of C26 and CT26 cancer models to induce cachexia using a syngeneic mouse model. After the inoculation of C26 and CT26 cells, the C26-inoculated mice displayed loss of bodyweight, while no effect on bodyweight was observed in the CT26 group despite a similar or even larger tumor growth. All muscles analyzed (gastrocnemius, soleus, plantaris, TA and EDL) were significantly smaller in C26 mice compared to control mice, while only the TA and gastrocnemius were significantly reduced in CT26 compared to control. Functionally, only the C26 mice showed a reduction in maximal isometric force of the plantar flexor muscles. Gene expression also differed between C26 and CT26. In the gastrocnemius muscle, MuRF1 and Atrogin-1 mRNA levels, markers of protein degradation, were elevated in C26, but not in CT26, when compared to non-tumor bearing mice. Expression of CD11b mRNA, a marker of innate immune cell infiltration, was only upregulated in C26. Interestingly, IL-6 and TNF-alpha mRNA were unchanged in both conditions. Leukocyte-type 12/15-LOX mRNA, a key lipoxygenase in polyunsaturated fatty acids, was remarkably downregulated in both C26 and CT26 groups. Overall, our results indicate that only C26 tumors led to loss of body weight and impaired skeletal muscle force output, in comparison to CT26 tumors. Although both C26 and CT26 cells exhibit cachectic effects, C26 show a higher capacity driving skeletal muscle wasting and loss of physical function. Funding: Start-up funding from Purdue University (JFM). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Lu et al. (Fri,) studied this question.