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DNA fragmentation occurs in skeletal muscle during tumor growth: A link with cancer cachexia?
M van Royen1, N Carbó, S Busquets
1Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain.
Abstract:
In two different experimental models of cancer cachexia, the rat Yoshida AH-130 ascites hepatoma and the mouse Lewis lung carcinoma, the implantation of the tumor caused a loss of body weight which was associated with a reduction in the weight of different skeletal muscles, as well as with their protein content. The decrease in protein content was accompanied by a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumor-bearing animals as compared with the non-tumor-bearing controls. Analysis of DNA fragmentation in skeletal muscle clearly showed enhanced laddering in the skeletal muscle of tumor-bearing animals, suggesting an apoptotic phenomenon. Interestingly, the degree of laddering (total DNA fragmented) increased with tumor burden. These results suggest that DNA fragmentation may be a primary event in cancer-associated cachexia.
Insights
Cancer cachexia in rats and mice involves significant body and skeletal muscle weight loss. DNA fragmentation in skeletal muscle, indicating apoptosis, increases with tumor burden, suggesting a key role in this condition.
Area of Science:
- Oncology
- Molecular Biology
- Physiology
Background:
- Cancer cachexia is a complex metabolic syndrome characterized by involuntary weight loss.
- Skeletal muscle wasting is a hallmark of cancer cachexia, significantly impacting patient prognosis and quality of life.
Purpose of the Study:
- To investigate the molecular mechanisms underlying skeletal muscle loss in experimental cancer cachexia models.
- To determine the role of DNA fragmentation and apoptosis in cancer-associated muscle wasting.
Main Methods:
- Utilized two established cancer cachexia models: Yoshida AH-130 ascites hepatoma in rats and Lewis lung carcinoma in mice.
- Assessed body weight, skeletal muscle weight, protein content, DNA content, and DNA fragmentation (laddering) in tumor-bearing and control animals.
Main Results:
- Tumor implantation led to significant body weight loss and reduced skeletal muscle weight and protein content.
- A decrease in skeletal muscle DNA content was observed, while the protein/DNA ratio remained unchanged.
- Enhanced DNA fragmentation (laddering) was detected in the skeletal muscle of tumor-bearing animals, with fragmentation levels correlating positively with tumor burden.
Conclusions:
- DNA fragmentation, indicative of apoptosis, appears to be a primary event in the pathogenesis of cancer-associated cachexia.
- These findings highlight the potential of targeting apoptotic pathways to mitigate skeletal muscle wasting in cancer patients.