Hyaluronan in Oncology

Another remarkable property of hyaluronan is that it enhances the effect of conventional anti-cancer drugs. HA allows their therapeutic doses to be reduced and consequently adverse toxicity to normal cells [83]. A large amount of hyaluronan and hyaluronidases is found in the extracellular matrix of the tumour. Many studies on the large number of various types of tumour cells demonstrated that high molecular weight HA can inhibit both proliferation and migration of tumour cells [80,81,83]. 

It is assumed that the tumour cells use of hyaluronidase as a molecular sabotage for the depolymerization of extracellular matrix polysaccharide macromolecules for two reasons first, to facilitate the invasion between normal cells and form metastasis in the tissues and secondly, to use the ability of low molecular weight degradation HA products to stimulate angiogenesis by sprouting blood vessels in tumour tissue. In order to discuss the molecular mechanisms by which hyaluronan affects the cell proliferation and tumour growth, it is important to examine the differences between normal and tumour cells [72]. 

Tumours represent a group of genetic diseases characterized by uncontrolled cell proliferation. The tumour cells typically are round or star-shaped and they are larger than normal cells. They have a different nucleus-cytoplasm ratio. The nucleus often contains not diploid, but polyploid or aneuploid sets of chromosomes. The differentiated cells are kept within certain tissues and do not intrude into the adjacent areas . They have a number of advantages over normal cells because of several characteristic features  

Increased rate of DNA and RNA synthesis by increased activity of the enzyme ribonucleotide reductase and a reduced rate of catabolism of purines and pyrimidines. 

Accelerated rate of glycolysis and increased lactate production. The activity ratio of key enzymes of glycolysis and respiration is changed and correlates with tumour growth 

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