Abstract
Increased polyamine concentrations in the blood and urine of cancer patients reflect the enhanced levels of polyamine synthesis in cancer tissues arising from increased activity of enzymes responsible for polyamine synthesis. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as cancer tissues, food, and intestinal microbiota. Because polyamines are indispensable for cell growth, increased polyamine availability enhances cell growth. However, the malignant potential of cancer is determined by its capability to invade to surrounding tissues and metastasize to distant organs. The mechanisms by which increased polyamine levels enhance the malignant potential of cancer cells and decrease anti-tumor immunity are reviewed. Cancer cells with a greater capability to synthesize polyamines are associated with increased production of proteinases, such as serine proteinase, matrix metalloproteinases, cathepsins, and plasminogen activator, which can degrade surrounding tissues. Although cancer tissues produce vascular growth factors, their deregulated growth induces hypoxia, which in turn enhances polyamine uptake by cancer cells to further augment cell migration and suppress CD44 expression. Increased polyamine uptake by immune cells also results in reduced cytokine production needed for anti-tumor activities and decreases expression of adhesion molecules involved in anti-tumor immunity, such as CD11a and CD56. Immune cells in an environment with increased polyamine levels lose anti-tumor immune functions, such as lymphokine activated killer activities. Recent investigations revealed that increased polyamine availability enhances the capability of cancer cells to invade and metastasize to new tissues while diminishing immune cells' anti-tumor immune functions.
Highlights
Polyamines, which include spermidine and spermine, are polycations with three or four amine groups
The increased blood and urinary polyamine levels are attributable to increased polyamine synthesis by cancer cells, since these increases can be abolished by complete eradication of tumors by surgery or radio-chemotherapy [2,3,4,5]
These results indicate that polyamines are produced by cancer tissues but are supplied from the intestinal lumen and together appear to influence polyamine levels in the body of cancer patients
Summary
Polyamines, which include spermidine and spermine, are polycations with three or four amine groups. Polyamines absorbed by the intestinal lumen are distributed to almost all organs and tissues in the body [29] as demonstrated by the increased blood polyamine levels in animals and humans produced in response to continuous enhanced polyamine intake for six and two months, respectively [30,31]. Decrease in blood polyamine levels can be successfully achieved by eliminating intestinal microbiota in addition to restricting food polyamines [33] Taken together, these results indicate that polyamines are produced by cancer tissues but are supplied from the intestinal lumen and together appear to influence polyamine levels in the body of cancer patients. The cellular response to hypoxia involves the stabilization and resultant increase in levels of hypoxia inducible factor-1 (HIF-1), a transcription factor that enhances gene expression to promote
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have