Abstract
Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and ApcMin/+. The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (μCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the ApcMin/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia.
Highlights
Colorectal cancer represents the third most common cancer in the United States and worldwide (Siegel et al, 2016) and is associated with the development of cachexia in up to 30% of the cases
We examined the effects of colorectal cancer growth on bone structure, and mechanical properties were determined by utilizing dual energy X-ray absorptiometry (DXA), micro computed tomography and three-point bending test
In order to investigate whether the growth of colorectal cancer associates with the development of cachexia and bone loss, we took advantage of three different in vivo models
Summary
Colorectal cancer represents the third most common cancer in the United States and worldwide (Siegel et al, 2016) and is associated with the development of cachexia in up to 30% of the cases. Cachexia, defined as loss of body weight and depletion of muscle mass (i.e., sarcopenia), with or without loss of fat tissue (Fearon et al, 2011), represents a devastating complication of cancer. Bone Loss in Colon Cancer Cachexia (Costelli and Baccino, 2003; Tisdale, 2009; Fearon et al, 2012). It has been estimated that up to 80% of cancer patients will develop cachexia over the course of their disease (Haehling and Anker, 2010). Cachexia is generally diagnosed in association with unintentional weight loss of at least 5% of initial weight and is normally accompanied by muscle weakness, fatigue, anorexia, changes in body composition (including lean and fat mass), increased inflammatory state, anemia and low levels of serum albumin. It has been shown that body and muscle weight loss positively correlate with enhanced mortality (Evans et al, 2008; Fearon et al, 2011)
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