Sialic acid (Neu5Ac, Neu5Gc, KDN) is a compound with the most complicated molecule structure of the monosaccharides.
Although sialic acid is a small molecule of about molecular weight 310, it consists of so many functional groups. Moreover, those functional groups take the equilibrium state peculiar to sugar according to conditions. When undertaking the synthetic chemistry of sialic acid for the first time, it makes it a little difficult.
The experiential conditions in each reaction becomes very important in order to synthesize the desired compound, because sialic acid has the property of being highly sensitive to reacting with various reagents.
This minireview, introduces a peculiar reaction and the fundamental reaction of Neu5Ac from among many which have already been reported. The chemical diversity of most typical N-acetylneuraminic acid in sialic acid is also described from each action by several simple reactions.

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Paradoxically, hyaluronan degradation can facilitate either cancer progression or tumor suppression. An attempt is made here to understand this apparent conundrum by examining the details of hyaluronan degradation. The catabolic pathway for hyaluronan is made up of a series of enzyme-catalyzed reactions. The hyaluronidases, the enzymes that degrade hyaluronan, do so in a step-wise fashion. The hyaluronan polymer decreases in size in quantum steps, and each polymer size has different biological activity. Each of the hyaluronidases and their respective products are reviewed for their role in supporting or suppressing malignant transformation, growth, invasion and metastatic spread of tumors. Such a systematic approach may clarify the mechanisms used by neoplastic cells in the course of cancer progression, resolve some of the apparent disparities, provide new prognostic markers, as well as potential targets for therapeutic intervention.

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Accumulating evidence indicates that hyaluronan (HA), a high molecular weight polymer that exists as a component of the extracellular matrix, is critically involved in tumor development and progression. HA synthesis is upregulated in various malignant tumors, resulting in the enhancement of tumor cell adhesion and migration, and mediation of signaling pathways. Furthermore, during tumor progression, HA that has been de-graded into oligosaccharides has been reported in the urine, blood or tumor tissue specimens of the patients with tumors. HA oligosaccharides are involved in functions such as angiogenesis, cell migration, and proliferation, and these functions are distinct from those of large HA polymers. We recently found that HA oligosaccharides of a certain size range induce proteolytic cleavage of CD44 from tumor cells (CD44 cleavage) and promote tumor cell migration in a CD44-dependent manner. Our results suggest that HA oligosaccharides serve as a physiological inducer of CD44 cleavage in vivo and reinforce the idea that they play an important role in tumor invasion. In this review, we will discuss the biological functions of HA oligosaccharides and their possible role in tumor development and progression.

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Hyaluronan is a major extracellular matrix component that is distributed widely in the body and plays a key role in maintaining the structural integrity of tissue. In addition to functioning as a supporting structure, the sugar chain regulates dynamic cellular behavior such as cell proliferation, motility and differentiation by acting on intracellular signaling pathways through interaction with receptors. Hyaluronan has attracted a great deal of attention because abnormal synthesis of this polysaccharide is often associated with cancer progression. Recently, the role of hyaluronan in promoting malignant cell transformation has been investigated in a series of studies in which the expression of the hyaluronan synthase genes were manipulated. This review outlines the close association between hyaluronan synthesis and cancer progression, citing recent findings in studies aimed at elucidating the mechanism of hyaluronan synthesis. I also address the possibility of developing drugs to prevent cancer progression based on the inhibition of hyaluronan synthesis.

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CD44 is a transmembrane adhesion molecule involved in cell-cell and cell-extracellular matrix interactions. It contains a functional hyaluronic acid-binding domain and serves as a major cell surface receptor for hyaluronic acid. It mediates recruitment of various types of cells and their motility in interstitial tissues of numerous organs. Cell adhesion mediated by CD44 has generally been assumed to enhance inflammatory response and cancer progression. Recent findings using CD44-deficient mice indicated that CD44 may not be an indispensable molecule for embryonic development and maintenance of life, but it remains clear that CD44 plays an important role in many pathological processes through its binding activity to hyaluronic acid. Glycosylation of CD44 is known to have a prominent effect on its hyaluronic acid binding activity. Usually CD44 expressed at the cell surface does not constitutively bind hyaluronic acid, and some activation process is necessary to attain effective hyaluronic acid binding. Recent findings indicated that specific changes in glycosylation of CD44 induced in stimulated cells play an essential role in the activation of hyaluronic acid binding. Two kinds of specific changes in its carbohydrate side chains were identified to be induced in stimulated cells, and figure heavily in the activation of hyaluronic acid binding; one is desialylation by an endogenous sialidase, and the other is enhancement of 6-sulfation in glycans carried by CD44.

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