Preparation, Characterization, and Inhibition of Hyaluronic Acid Oligosaccharides in Triple-Negative Breast Cancer.

Wenwei Han,Youjing Lv,Xiangyan Chen,Xia Zhao,Lili Song,Yingdi Wang

doi:10.3390/biom9090436

Abstract

Hyaluronic acid (hyaluronan, HA) is a critical component of the extracellular matrix and plays an important biological function of interacting with different molecules and receptors. In this study, both odd- and even-numbered HA oligosaccharides (HAOs) with specific degrees of polymerization (DP) were prepared by different hydrochloric acid hydrolyses, and their structures were characterized by means of HPLC, ESI-MS, and NMR. The data show that the odd-numbered HAOs (DP3-11) have a glucuronic acid reducing end, while the even-numbered HAOs (DP2-10) have an N-acetylglucosamine reducing end. Biological evaluations indicated that all HAOs significantly inhibited the growth and migration of triple-negative breast cancer (TNBC) MDA-MB-231 cells. Among these oligosaccharides, the HA tetrasaccharide (DP4) was confirmed to be the minimum fragment necessary to inhibit MDA-MB-231 cells. Our data suggest that HAOs have potential value in the treatment of TNBC.

Highlights

Hyaluronic acid is a major component of the extracellular matrix and is a nonsulfated glycosaminoglycan composed of β-N-acetylglucosamine (GlcNAc)-(1,3)-β-glucuronic acid (GlcA)-(1,4) -repeating units
The Hyaluronic Acid (HA) tetrasaccharide (HAO-DP4) was confirmed to be the minimum fragment necessary to inhibit Triple-negative breast cancer (TNBC). These similar results were demonstrated in other GAG oligosaccharides, for example, tetra oligosaccharide is the shortest heparan sulfate that binds to fibroblast growth factor 2 (FGF2) [43]
Further studies are needed to confirm these hypotheses. Both odd- and even-numbered HA oligosaccharides (HAOs) were obtained by bond-selective degradation for the first time

Summary

Introduction

Hyaluronic acid (hyaluronan, HA) is a major component of the extracellular matrix and is a nonsulfated glycosaminoglycan composed of β-N-acetylglucosamine (GlcNAc)-(1,3)-β-glucuronic acid (GlcA)-(1,4) -repeating units. Accumulating evidence suggests that HA is involved in a variety of cellular processes, including cell adhesion, migration, and proliferation [1,2]. HA was reported to have interacted with various cell surface receptors such as receptors for HA-mediated motility (RHAMM) [3], cluster of differentiation 44 (CD44) [4,5,6], lymphatic vessel endothelial hyaluronan receptor (LYVE1) [7], and toll-like receptors (TLRs) [8]. HA plays an important role in cancer initiation, proliferation, metastasis, and progression [9,10,11]. Cell culture studies showed that the invasive breast cancer cells synthesize and accumulate larger amounts of HA than normal tissue, especially remarkable in TNBC cells [15].

Methods

Results

Discussion

Conclusion