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Review
. 2017 Jan;143(1):1-16.
doi: 10.1007/s00432-016-2213-5. Epub 2016 Aug 17.

Hyaluronic acid in digestive cancers

Ruo-Lin Wu  1   2 , Lei Huang  3   4 , Hong-Chuan Zhao  1 , Xiao-Ping Geng  5
Affiliations
Review

Hyaluronic acid in digestive cancers

Ruo-Lin Wu et al. J Cancer Res Clin Oncol. 2017 Jan.

Abstract

Purpose: Hyaluronan (HA), an extracellular and peri-cellular glycosaminoglycan with a large molecular weight, plays an important role in cancer growth and metastasis. The aim of this study was to summarize the biological roles and regulation of HA and small HA fragments, and their metabolismn enzymes and receptors in human digestive cancers.

Methods: A systematic literature search mainly focusing on the biological roles of HA in the development and progression of human digestive cancers was performed using electronic databases.

Results: The correlation between HA accumulation and tumor progression has been shown in various digestive cancers. HA and HA fragment-tumor cell interaction could activate the downstream signaling pathways, promoting cell proliferation, adhesion, migration and invasion, and inducing angiogenesis, lymphangiogenesis, epithelial-mesenchymal transition, stem cell-like property, and chemoradioresistance in digestive cancers.

Conclusions: A better insight into the mechanism of HA and HA fragment involvement in digestive cancer progression might be useful for the development of novel biomarkers and therapeutic strategies.

Keywords: Digestive cancer; Epithelial–mesenchymal transition; Hyaluronan; Metastasis; Prognosis; Receptor; Tumor growth.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Effect of HA–CD44 interaction on digestive cancer invasion and metastasis. HA binds to cell surface CD44, and induces multiple RTKs (including ErbB2) activation and signaling complex assembly (including PI3K), which promotes digestive cancer cell survival and tumor progression. CD44 cluster of differentiation 44, RTK receptor tyrosine kinase, Vav2 guanine nucleotide exchange factor, Grb2 growth factor receptor-bound protein 2, ErbB2 erb-b2 receptor tyrosine kinase 2, Hsp90/cdc-37 heat–shock protein 90/Hsp90 co-chaperone Cdc37, Gab-1 growth factor receptor-bound 2 (Grb2)-associated binder-1, Ezrin cytovillin or villin-2, Src proto-oncogene tyrosine-protein kinase Src, PI3K phosphoinositide 3-kinase, Akt protein kinase B, Stat3 signal transducer and activator of transcription 3. COX-2/PEG2 prostaglandin-endoperoxide synthase 2, EMT epithelial–mesenchymal transition
Fig. 2
Fig. 2
Biological effects of sHA on cell surface receptors in digestive cancers. sHA predominantly produced from hyaluronidase digestion, interacts with different cell surface receptors including CD44, LYVE-1, and TLR-4, which regulates the indicated tumor biological effects. HMW-HA, high molecular weight hyaluronic acid; sHA small hyaluronic acid fragments; CD44 cluster of differentiation 44; LYVE-1 lymphatic endothelial cells hyaluronic acid receptor 1; TLR-4 Toll-like receptor-4; PKCα/β II protein kinase C α/β II; ERK1/2 extracellular signal-regulated kinases; PI3K phosphoinositide 3-kinase; Akt protein kinase B
See this image and copyright information in PMC

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