Hudgins W R, Orth D N, Stromberg K
Laboratory of Viral Carcinogenesis, National Cancer Institute-Frederick Cancer Research Facility, Maryland 21701.
Cancer Res. 1988 Mar 15;48(6):1428-34.
Epidermal growth factor (EGF) receptor-binding peptides from the urine of tumor patients have been reported to differ in molecular weight and relative hydrophobicity from those of normal individuals. Nude rats bearing human large cell lung carcinomas or chondrosarcomas and non-tumor-bearing sibling control rats were used to investigate the contributions of tumor and host to urinary EGF-related peptide growth factors. Peptides were adsorbed from urine onto methyl-bonded silica and eluted according to their relative hydrophobicity by a stepwise gradient of aqueous acetonitrile. Total EGF receptor-binding activity relative to urinary creatine was elevated in the urine of only one group of tumor-bearing rats. However, the proportion of relatively hydrophilic activity was increased markedly in all three groups of tumor-bearing rats. Rats bearing a large cell lung cancer excreted unusually hydrophilic Mr 6000 peptides that were chromatographically similar to transforming growth factor alpha on reverse phase high performance liquid chromatography but proved to be rat EGF by radioimmunoassay (RIA). EGF receptor-binding activity that was common to the urine of tumor-bearing animals regardless of tumor type, but more hydrophilic than that from control rats, had Mr 60,000, 30,000, 12,000, and 4,000 to 7,000 components. All reacted fully in the rat EGF RIA and were negative for human EGF and transforming growth factor alpha by RIA. A more hydrophobic fraction of EGF receptor-binding activity, common to control and tumor-bearing animals, contained Mr 33,000, 5,000 to 7,000, and 2,000 to 5,000 components. High performance liquid chromatography and gel electrophoresis of the Mr 33,000 activity revealed a high molecular weight rat EGF comparable to that reported in human urine. No human EGF or transforming growth factor alpha was detected by RIA in any of the active fractions from tumor-bearing rat urine. Thus, all EGF receptor-binding activity appeared to derive from rat EGF produced by the rat host and not by the xenografted tumors.
据报道，肿瘤患者尿液中的表皮生长因子（EGF）受体结合肽在分子量和相对疏水性方面与正常个体不同。用人的大细胞肺癌或软骨肉瘤裸鼠以及无肿瘤的同窝对照鼠来研究肿瘤和宿主对尿中EGF相关肽生长因子的影响。肽从尿液中吸附到甲基键合硅胶上，并通过乙腈水溶液的逐步梯度根据其相对疏水性进行洗脱。相对于尿肌酐，仅一组荷瘤大鼠尿液中的总EGF受体结合活性升高。然而，在所有三组荷瘤大鼠中，相对亲水性活性的比例均显著增加。携带大细胞肺癌的大鼠排泄出异常亲水性的6000道尔顿肽，在反相高效液相色谱上其色谱行为与转化生长因子α相似，但通过放射免疫测定（RIA）证明是大鼠EGF。荷瘤动物尿液中常见的EGF受体结合活性，无论肿瘤类型如何，但比对照大鼠的更具亲水性，其成分的分子量为60,000、30,000、12,000以及4,000至7,000。所有这些成分在大鼠EGF RIA中均有完全反应，而在RIA中对人EGF和转化生长因子α呈阴性。对照动物和荷瘤动物共有的EGF受体结合活性的一个更疏水部分，包含分子量为33,000、5,000至7,000以及2,000至5,000的成分。对分子量为33,000的活性成分进行高效液相色谱和凝胶电泳分析，发现了一种与人类尿液中报道的高分子量大鼠EGF相当的物质。在荷瘤大鼠尿液的任何活性部分中，通过RIA均未检测到人EGF或转化生长因子α。因此，所有EGF受体结合活性似乎都源自大鼠宿主产生的大鼠EGF，而非移植的肿瘤。
