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The mechanisms by which polyamines accelerate tumor spread

DOI: 10.1186/1756-9966-30-95

Keywords: Polyamine, metastasis, spermine, spermidine, LAK, LFA-1

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Polyamines, which include spermidine and spermine, are polycations with three or four amine groups. Almost all cells can produce polyamines, but their production is especially high in rapidly growing cells. Polyamine concentrations are often increased in the blood and urine of cancer patients, and these increased levels have been shown to correlate with poor prognosis [1]. 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 [2-5]. The capacity of cancer tissue to produce abundant polyamines likely contributes to cancer cells' enhanced growth rates because polyamines are indispensable for cellular growth, which may at least partially explain why cancer patients with increased polyamine levels have a poorer prognosis [4-9]. However, an important factor that determines the malignant potential of cancer cells is the capability of cells to invade to surrounding tissues and to metastasize to distant organs. Therefore, it is important to understand the role of polyamines in cancer invasion and metastasis. In this review, recent experimental results from our and other groups are discussed.The natural polyamines, spermidine, and spermine, are found in almost every living cell at high micromolar to low millimolar quantities [10]. Polyamines are synthesized from arginine and s-adenosylmethionine with arginase converting arginine to ornithine, and ornithine decarboxylase (ODC) catalyzing ornithine decarboxylation to form putrescine, a polyamine precursor containing two amine groups (Figure 1). Polyamines are involved in diverse functions involved in cell growth and differentiation, such as DNA synthesis and stability, regulation of transcription, ion channel regulation, and protein phosphorylation [11-14].Intracellular spermine and spermidine are degraded by spermidine/spermine N1-acetyltransferase (SSAT) and N


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