Methylthioadenosine phosphorylase deficiency in human non-small cell lung cancers

• Published in: Cancer research (Chicago, Ill.) Vol. 53; no. 5; pp. 1098 - 1101
• Main Authors: NOBORI, T, SZINAI, I, AMOX, D, PARKER, B, OLOPADE, O. I, BUCHHAGEN, D. L, CARSON, D. A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.03.1993
• Subjects: Adult; Aged; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - enzymology; Deoxyadenosines - pharmacology; Deoxyadenosines - therapeutic use; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Male; Medical sciences; Middle Aged; Pneumology; Purine-Nucleoside Phosphorylase - deficiency; Tetrahydrofolates - pharmacology; Tetrahydrofolates - therapeutic use; Thionucleosides - pharmacology; Thionucleosides - therapeutic use; Tumor Cells, Cultured; Tumors of the respiratory system and mediastinum; Human; Purine nucleoside; Respiratory disease; Enzyme; Exploration; Biosynthesis; Malignant tumor; In vitro; Bronchopulmonary; 5'-Methylthioadenosine phosphorylase; Established cell line; Tumor cell; Non small cell carcinoma
• ISSN: 0008-5472; 1538-7445

Methylthioadenosine (MeSAdo) phosphorylase, a purine metabolic enzyme, is present in all normal mammalian tissues. A deficiency of this enzyme has been reported in some human leukemias and lymphomas and in a few solid tumors. In the present study, a specific immunoassay was used to assess the enzyme levels in human non-small cell lung cancer cell lines and primary tumors. We also tested the effects of MeSAdo phosphorylase-selective chemotherapy on the in vitro growth of enzyme-positive and enzyme-negative lung cancer cell lines. Of 29 non-small cell lung cancers, 9 (6 cell lines and 3 primary tumors, 31%) lacked detectable immunoreactive enzyme protein. Both 5,10-dideazatetrahydrofolate, an inhibitor of de novo purine synthesis, and methionine depletion, combined with MeSAdo, prevented the growth of the enzyme-negative non-small cell lung cancer cells under conditions in which enzyme-positive cells utilized MeSAdo to endogenously synthesize purine nucleotides and methionine. Our data suggest that MeSAdo phosphorylase deficiency is frequently found in non-small cell lung cancers and can be exploited in designing enzyme-selective chemotherapy.