During neoplastic development, several aspects of the regulation of
polyamine synthesis undergo profound changes. In extrahepatic mammalian tissues in which the
urea cycle is not functioning,
arginase is believed to supply the cell with
ornithine, a non-
protein amino acid that is a precursor for biosynthesis of
polyamines. Because the activity of
ornithine decarboxylase and
polyamine levels have been shown to be elevated during
carcinogenesis, we decided to investigate the role of
arginase in the development of malignant
tumors of the human skin and to examine whether
arginase activity and
ornithine level can be used as
biologic markers for distinguishing patients with
squamous cell cancer from patients with
basal cell cancer. For this purpose, we studied tissue
arginase activity and
ornithine level in
tumor and adjacent normal tissues in 16 patients (55 +/- 10 years of age) with malignant skin
tumors (8 of which were
squamous cell cancers and 8 of which were
basal cell cancers). The mean
arginase activity and
ornithine levels in
tumor 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
arginase activity levels in squamous cell and
basal cell cancers of the human skin were 18.49 +/- 10.47 U/mg
protein and 16.63 +/- 6.00 U/mg
protein, respectively. The mean
ornithine levels in squamous cell and
basal cell cancers of the human skin were 42.45 +/- 19.10 nmol/mg
protein and 39.33 +/- 10.19 nmol/mg
protein, respectively. Our results indicated that (1)
arginase activity and
ornithine levels are elevated in squamous cell and
basal cell cancers of the human skin; (2) the increased activity of
arginase and hence the elevated levels of
ornithine may be important in the development of malignant
tumors of the human skin; and (3) although
arginase activity and
ornithine level may be useful for distinguishing patients with malignant skin
tumors from healthy subjects, they cannot be used as
biologic markers for distinguishing patients with
squamous cell cancer from patients with
basal cell cancer.