Abstract
Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 104 B16F10 melanoma cells or PBS as a Sham negative control. Tumor growth was monitored during a period of 28 days. Compared to Sham mice, tumor group depicts a loss of skeletal muscle, as well as significantly reduced muscle grip strength and epididymal fat mass. This data are in agreement with mild to severe catabolic host response promoted by elevated serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and lactate dehydrogenase (LDH) activity. Tumor implantation has also compromised general locomotor activity and decreased exploratory behavior. Likewise, muscle loss, and elevated inflammatory interleukin were associated to muscle strength loss and locomotor activity impairment. In conclusion, our data demonstrated that subcutaneous B16F10 melanoma tumor-driven catabolic state in response to a pro-inflammatory environment that is associated with impaired skeletal muscle strength and decreased locomotor activity in tumor-bearing mice.
Highlights
Cancer cachexia is a complex syndrome characterized by progressive weight loss, anorexia, muscle loss and weakness
Elevated inflammatory interleukins and muscle wasting during tumor development can significantly modulate muscle strength and locomotor capacity in tumorbearing mice, some of the most critical endpoints associated with cancer morbidity and mortality (Christensen et al, 2014)
Despite early stages melanomas are not related with weight loss, the appearance of metastatic and/or solid tumor melanoma is related to cachexia development (Kawamura et al, 1999b; Das et al, 2011)
Summary
Cancer cachexia is a complex syndrome characterized by progressive weight loss, anorexia, muscle loss and weakness. Melanoma B16F10 Compromises Muscle Function are associated with weight loss, hypercatabolism, reduced food intake and muscle loss in cancer patients (De Larichaudy et al, 2012; Yuan et al, 2015). Elevated inflammatory interleukins and muscle wasting during tumor development can significantly modulate muscle strength and locomotor capacity in tumorbearing mice, some of the most critical endpoints associated with cancer morbidity and mortality (Christensen et al, 2014). Recent data has been demonstrated lung, gastrointestinal tract, extra-regional lymph nodes, liver and prostate are the principal target of metastatic melanoma; all of than with elevated rate of cachexia (40 to 80%) and mortality (von Haehling et al, 2016)
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