Significance of arginase and ornithine in malignant tumors of the human skin

During neoplastic development, several aspects of the regulation of polyami ne synthesis undergo profound changes. In extrahepatic mammalian tissues in which the urea cycle is not functioning, arginase is believed to supply th e cell with ornithine, a non-protein amino acid that is a precursor for bio synthesis of polyamines. Because the activity of ornithine decarboxylase an d polyamine levels have been shown to be elevated during carcinogenesis, we decided to investigate the role of arginase in the development of malignan t tumors of the human skin and to examine whether arginase activity and orn ithine level can be used as biologic markers for distinguishing patients wi th squamous cell cancer from patients with basal cell cancer. For this purp ose, we studied tissue arginase activity and ornithine level in tumor and a djacent normal tissues in 16 patients (55 +/- 10 years of age) with maligna nt skin tumors (8 of which were squamous cell cancers and 8 of which were b asal cell cancers). The mean arginase activity and ornithine levels in tumo r tissues (total) were 17.75 +/- 8.54 U/mg protein and 40.89 +/- 14.88 nmol /mg protein, respectively, versus 3.69 +/- 1.71 U/mg protein and 12.98 +/- 6.21 nmol/mg protein, respectively, for normal tissues. The mean specific a rginase activity levels in squamous cell and basal cell cancers of the huma n skin were 18.49 +/- 10.47 U/mg protein and 16.63 +/- 6.00 U/mg protein, r espectively. The mean ornithine levels in squamous cell and basal cell canc ers of the human skin were 42.45 +/- 9.10 nmol/mg protein and 39.33 +/- 10. 19 nmol/mg protein, respectively. Our results indicated that (1) arginase a ctivity and ornithine levels are elevated in squamous cell and basal cell c ancers of the human skin (2) the increased activity of arginase and hence t he elevated levels of ornithine may be important in the development of mali gnant tumors of the human skin; and (3) although arginase activity and orni thine level may be useful for distinguishing patients with malignant skin t umors from healthy subjects they cannot be used as biologic markers for dis tinguishing patients with squamous cell cancer from patients with basal cel l cancer.