Fishman P, Bar-Yehuda S, Vagman L
Laboratory of Clinical and Tumor Immunology, The Felsenstein Medical Research Center, Tel-Aviv University, Rabin Medical Center, Petach-Tikva, Israel.
Cancer Res. 1998 Jul 15;58(14):3181-7.
In this study, we investigated the basis of the resistance of muscles to tumor metastases. We found that a low molecular weight fraction (Mr <3000) of skeletal muscle cell-conditioned medium (MCM) markedly inhibits the proliferation of carcinoma, sarcoma, or melanoma cell lines in vitro. The MCM exerts a cytostatic effect on tumor cell growth and arrests the cells in G0/G1 of the cell cycle. However, normal cell proliferation of cells such as bone marrow cells or fibroblasts was found to be refractory to the influence of the MCM. A reduction in melanoma growth was observed in mice treated with the MCM. Adenosine was identified as one of the active components in the MCM by using high-performance liquid chromatography separations, mass spectra, and nuclear magnetic resonance analyses. At a concentration of 4 microM, equal to that found in the MCM, adenosine inhibits the proliferation of tumor cell lines (Nb2 lymphoma, K-562 leukemia, and LNCaP prostate carcinoma cells) while stimulating the proliferation of normal murine bone marrow cells. By similar methods, additional inhibitory components were detected in the MCM in a molecular mass range of 600-800 Da. The ability of adenosine and other low molecular weight components to specifically inhibit tumor cell growth in vitro and in vivo may account for the resistance of muscle to tumor metastases.
在本研究中，我们调查了肌肉对肿瘤转移具有抗性的基础。我们发现，骨骼肌细胞条件培养基（MCM）的低分子量组分（Mr <3000）在体外能显著抑制癌细胞、肉瘤细胞或黑色素瘤细胞系的增殖。MCM对肿瘤细胞生长发挥细胞抑制作用，并使细胞停滞在细胞周期的G0/G1期。然而，发现骨髓细胞或成纤维细胞等正常细胞的增殖对MCM的影响具有抗性。在用MCM处理的小鼠中观察到黑色素瘤生长有所减少。通过高效液相色谱分离、质谱和核磁共振分析，腺苷被鉴定为MCM中的活性成分之一。在浓度为4 microM（与MCM中发现的浓度相同）时，腺苷抑制肿瘤细胞系（Nb2淋巴瘤、K-562白血病和LNCaP前列腺癌细胞）的增殖，同时刺激正常小鼠骨髓细胞的增殖。通过类似方法，在MCM中还检测到分子量范围为600 - 800 Da的其他抑制性成分。腺苷和其他低分子量成分在体外和体内特异性抑制肿瘤细胞生长的能力，可能解释了肌肉对肿瘤转移的抗性。
