2006
DOI: 10.1074/jbc.m506740200
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Tumor Cells Enhance Their Own CD44 Cleavage and Motility by Generating Hyaluronan Fragments

Abstract: Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that interacts with cell-surface receptors, including CD44. Although HA usually exists as a high molecular mass polymer, HA of a much lower molecular mass that shows a variety of biological activities can be detected under certain pathological conditions, particularly in tumors. We previously reported that low molecular weight HAs (LMW-HAs) of a certain size range induce the proteolytic cleavage of CD44 from the surface of tumor cells and promote tum… Show more

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Cited by 128 publications
(102 citation statements)
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“…These oligosaccharides are most likely generated by digestion with Chnase in vivo because their reducing terminal sugar residues are GalNAc. Note that HA oligosaccharides liberated by digestion with hyaluronidases have biological activities, such as induction of the transcription of metalloproteases (37), enhancement of tumor cell motility (38), and inhibition of the tumorigenicity of cancer cells (39). A disaccharide derived from CS was also demonstrated to promote recovery of the central nervous system by modulating both neuronal and microglial behavior (40).…”
mentioning
confidence: 99%
“…These oligosaccharides are most likely generated by digestion with Chnase in vivo because their reducing terminal sugar residues are GalNAc. Note that HA oligosaccharides liberated by digestion with hyaluronidases have biological activities, such as induction of the transcription of metalloproteases (37), enhancement of tumor cell motility (38), and inhibition of the tumorigenicity of cancer cells (39). A disaccharide derived from CS was also demonstrated to promote recovery of the central nervous system by modulating both neuronal and microglial behavior (40).…”
mentioning
confidence: 99%
“…Cleavage of the extracellular region is promoted by various pathways, such as those activated by extracellular Ca 2ϩ influx, protein kinase C, Rho family small GTPases, and Rac and Ras oncoproteins (8,9). Recently, it was reported that small HA oligosaccharides, generated by tumor cells constitutively expressing hyaluronidases, could induce the cleavage of the extracellular region and promote tumor migration in a CD44-dependent fashion (6,10).…”
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confidence: 99%
“…High levels of HAse activity have been found in various tumors. 49,50 Its presence in dialysis tubes increased the cisplatin release rate, due to enzymatic degradation of HA. Consistently, the initial release within the first 30 minutes increased from 26.2% to 42 International Journal of Nanomedicine 2014:9…”
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confidence: 99%