Demonstration of an Altered S-Adenosylmethionine Synthetase in Human Malignant Tumors Xenografted Into Athymic Nude Mice

Abstract

S-Adenosyimethionine synthetase isoenzymes (EC 2.5.1.6) were studied in human malignant tumors xenografted into athymic nude mice and were studied in normal human and rat tissues. The tumors included 7 melanomas; 4 colon carcinomas; 3 each of mammary, cervical, and ovary carcinomas; 2 each of lung carcinomas and sarcomas; and 1 each of lymphoma and stomach and nasopharyngeal carcinomas. The presence of an altered intermediate Michaelis constant (K_m) isoenzyme, previously shown to be a unique characteristic of rat neoplastic tissues, in these tumors was invariably detectable, though the presence of the low-K_m isoenzyme characteristic of the enzyme of normal tissues was also evident in many of these tumors. Only tumors demonstrating high rates of growth were devoid of the Iow-K_m isoenzyme. The low-K_m isoenzyme was the only enzyme detectable in many normal human and rat tissues. Thus this isoenzyme was probably the common enzyme of all tissues. Some additional organ-specific isoenzymes were found, e.g., in the liver and lactating mammary gland. The low-K_m isoenzyme in malignant tumors was altered to assume a considerably higher K_m value, and this alteration appeared to be a common aberration of malignant tumors.