Progressive decrease of phosphocreatine, creatine and creatine kinase in skeletal muscle upon transformation to sarcoma
Progressive decrease of phosphocreatine, creatine and creatine kinase in skeletal muscle upon transformation to sarcoma
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DOI：
10.1111/j.1742-4658.2008.06475.x
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发表时间：
2008-06-01
期刊：
影响因子：
5.4
通讯作者：
Ray, Manju
中科院分区：
文献类型：
--
作者：
Patra, Subrata;Bera, Soumen;Ray, Manju
在脊椎动物中，磷酸肌酸和ATP根据细胞能量需求通过肌酸激酶的可逆反应不断相互转化。肉瘤组织及其正常的对应物，富含肌酸的骨骼肌，是研究肌酸和肌酸激酶随恶性肿瘤进展状态的良好来源材料。我们用3-甲基胆蒽或活的肉瘤180细胞分别注入小鼠一条后腿，诱导腿部肌肉肉瘤形成。肌酸、磷酸肌酸和肌酸激酶异构体水平随着恶性肿瘤的进展而下降，并在肉瘤发展的最后阶段达到非常低的水平；所有这些参数在同一动物的未受影响的对侧腿肌肉中保持不变。与同一样本的远端非恶性部分相比，人类肉瘤、胃和结肠腺癌的直接恶性部分的肌酸和肌酸激酶水平也显著降低。在小鼠中，抗细胞质肌型肌酸激酶和线粒体肌酸激酶抗体的免疫印迹显示，随着恶性肿瘤的进展，这两种同工型都减少了。肌型肌酸激酶和线粒体肌酸激酶mRNA的表达也严重下调。在人肉瘤中，这两种亚型也检测不到。在人胃和结肠腺癌中，脑型肌酸激酶被发现下调，而普遍存在的线粒体肌酸激酶则上调。肉瘤中肌酸和肌酸激酶同型异构体水平的显著下降表明：(a)在肉瘤进展过程中，真正的肌肉表型丢失了，(b)这些参数可以用作该组织中恶性肿瘤的诊断标记和预后指标。
In vertebrates, phosphocreatine and ATP are continuously interconverted by the reversible reaction of creatine kinase in accordance with cellular energy needs. Sarcoma tissue and its normal counterpart, creatine-rich skeletal muscle, are good source materials to study the status of creatine and creatine kinase with the progression of malignancy. We experimentally induced sarcoma in mouse leg muscle by injecting either 3-methylcholanthrene or live sarcoma 180 cells into one hind leg. Creatine, phosphocreatine and creatine kinase isoform levels decreased as malignancy progressed and reached very low levels in the final stage of sarcoma development; all these parameters remained unaltered in the unaffected contralateral leg muscle of the same animal. Creatine and creatine kinase levels were also reduced significantly in frank malignant portions of human sarcoma and gastric and colonic adenocarcinoma compared with the distal nonmalignant portions of the same samples. In mice, immunoblotting with antibodies against cytosolic muscle-type creatine kinase and sarcomeric mitochondrial creatine kinase showed that both of these isoforms decreased as malignancy progressed. Expressions of mRNA of muscle-type creatine kinase and sarcomeric mitochondrial creatine kinase were also severely downregulated. In human sarcoma these two isoforms were undetectable also. In human gastric and colonic adenocarcinoma, brain-type creatine kinase was found to be downregulated, whereas ubiquitous mitochondrial creatine kinase was upregulated. These significantly decreased levels of creatine and creatine kinase isoforms in sarcoma suggest that: (a) the genuine muscle phenotype is lost during sarcoma progression, and (b) these parameters may be used as diagnostic marker and prognostic indicator of malignancy in this tissue.