Progressive decrease of phosphocreatine, creatine and creatine kinase in skeletal muscle upon transformation to
Subrata Patra1, Soumen Bera, Soumya SinhaRoy
1Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, India.
The FEBS Journal
|May 20, 2008
Summary
Creatine and creatine kinase levels significantly decrease during sarcoma progression, indicating a loss of muscle phenotype. These markers may serve as diagnostic and prognostic indicators for malignancy.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Vertebrates utilize creatine kinase to interconvert phosphocreatine and ATP, crucial for cellular energy demands.
- Skeletal muscle, rich in creatine, and sarcoma are valuable models for studying malignancy-associated changes in creatine metabolism.
Purpose of the Study:
- To investigate the changes in creatine, phosphocreatine, and creatine kinase isoforms during sarcoma progression in mice and human tissues.
- To evaluate the potential of these molecules as diagnostic markers and prognostic indicators of malignancy.
Main Methods:
- Experimentally induced sarcoma in mouse leg muscle using 3-methylcholanthrene or sarcoma 180 cells.
- Analyzed creatine, phosphocreatine, and creatine kinase isoform levels (protein and mRNA) in mouse and human tumor tissues.
- Utilized immunoblotting and mRNA expression analysis.
Main Results:
- Creatine, phosphocreatine, and creatine kinase isoform levels markedly decreased with sarcoma progression in mice, remaining unchanged in contralateral muscle.
- Human sarcoma, gastric, and colonic adenocarcinoma showed significantly reduced creatine and creatine kinase levels in malignant versus nonmalignant portions.
- Specific creatine kinase isoforms (muscle-type, sarcomeric mitochondrial) were downregulated in mice and undetectable in human sarcoma; brain-type and ubiquitous mitochondrial isoforms showed altered expression in human adenocarcinomas.
Conclusions:
- Decreased creatine and creatine kinase levels in sarcoma suggest a loss of the genuine muscle phenotype during malignancy progression.
- These parameters show potential as diagnostic markers and prognostic indicators for sarcoma and other adenocarcinomas.
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