Variant forms of rat epidermal growth factor present in the urine of nude rats bearing human tumors.
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.
Hudgins
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WR
Laboratory of Viral Carcinogenesis, National Cancer Institute-Frederick Cancer Research Facility, Maryland 21701.
Orth
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DN
Stromberg
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K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004815:Epidermal Growth Factor / Q000276:immunology / Q000652:urine*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000652:urine*; D010455:Peptides / Q000276:immunology / Q000652:urine*; D011863:Radioimmunoassay; D051381:Rats; D015291:Transforming Growth Factors; D014183:Transplantation, Heterologous
D010455:Peptides; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D066246:ErbB Receptors