Polyamine biosynthetic activity in normal and neoplastic human colorectal tissues

Abstract

Polyamine biosynthetic activity was assessed in various colorectal tissue samples consisting of noninvolved mucosa, benign adenomatous polyps and adenocarcinomas taken at surgery from a total of 40 patients. Ornithine decarboxylase (ODC) displayed a gradient of enzyme activity (i.e., adenocarcinoma greater than polyps greater than mucosa) which seemed to correlate positively with the neoplastic status of the tissue. In 10 of the patients, samples were obtained for all three tissue types. Five of these exhibited a clear repetition of the trends in enzyme activity seen with the mixed patient tissue sampling whereas the remainder differed by having the highest ODC activity in the polyps. In nine of the ten cases, ODC activity was substantially lower in the mucosa than in either of the neoplastic lesions. Trends in enzyme activity were the same for tissues obtained from either the colon or rectum. The ODC activity in adenocarcinomas could not be correlated with histologic differentiation, stage or site of the disease, however, in samples from female patients (all postmenopausal) the activity was elevated over normal mucosa to a greater extent (ten-fold) than in male patients (seven-fold). S-adenosylmethionine decarboxylase activity was assessed in 27 of the 40 patients and found to follow the same distribution as ODC; however, the mean value differences +/- SEM between tissues were less distinct. In general, tissue polyamine pool analysis of these same specimens reflected the levels of ornithine and S-adenosylmethionine decarboxylase activities. Overall, the data reveal an increase in polyamine biosynthetic activity in colorectal neoplasms, relative to surrounding mucosa, which may correlate with (1) progression of the neoplastic process, (2) the proportion of proliferating cells, (3) the rate of cell proliferation, or (4) a combination of two or all of these possibilities.

Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis

“…[19][20][21][22][23] In human beings, ODC and polyamine levels are elevated in neoplasms compared with normal-appearing adjoining mucosa. [24][25][26][27][28][29][30][31][32][33] In addition, these compounds are elevated in the normal mucosa of gene carriers of familial adenomatous polyposis (FAP) before the development of adenomas, suggesting a role for these compounds in tumorigenesis in this disorder.…”

Metabolic and Antiproliferative Consequences of Activated Polyamine Catabolism in LNCaP Prostate Carcinoma Cells

“…Thus, ornithine decarboxylase (ODC) 1 and S-adenosylmethionine decarboxylase (SAMDC) control biosynthesis, a polyamine transport system modulates uptake, and spermidine/spermine N 1 -acetyltransferase (SSAT) regulates polyamine catabolism and export out of the cell. Neoplastic cell growth is associated with elevated polyamine biosynthetic activity, even when the surrounding normal tissue itself is rapidly proliferating, such as the intestinal mucosa (2)(3)(4). Thus, the rationale for targeting polyamines in antitumor strategies relates to their critical role in supporting neoplastic cell growth and to the overexpression of biosynthetic enzymes in tumor versus normal tissues (3,5,6).…”

Ornithine Decarboxylase Activity as a Prognostic Marker for Colorectal Cancer

“…ODe activity in biopsy specimens was approximately two to ten fold higher than that in operative specimens (data not shown). Porter et al 13 ) reported similar results with a comparison of biopsy and surgical specimens, and recommended that ODe activity be measured using biopsy samples. The time required for surgical tissue resection may be sufficient to account for substantial loss in enzyme activity.…”

“…It has been reported that there is a negative correlation between ODe activity and progression or stage of colorectal cancer I4 ). On the other hand, a positive correlation between ODe activity and TNM classification was reported 13 ). The difference in tissue samples (ie.…”