Hydroxyethyl chitosan hydrogels for enhancing breast cancer cell tumorigenesis

Int J Biol Macromol. 2021 Aug 1:184:768-775. doi: 10.1016/j.ijbiomac.2021.06.110. Epub 2021 Jun 24.

Abstract

Polysaccharide hydrogels are promising candidate matrices for recapitulating the characteristics of extracellular matrix (ECM) in breast tumors in terms of their structure and composition. Herein, to obtain an ECM-mimetic matrix, hydroxyethyl chitosan (HECS) hydrogels were prepared through Schiff-base crosslinking reaction using dialdehyde hyaluronic acid as crosslinker. The obtained HECS hydrogels displayed a highly porous structure, a stiffness comparable to that of breast tissue, and a fast water-absorption speed. The amount of crosslinker had great effects on the swelling and rheological behaviors of the HECS hydrogels. Preliminary results from in vitro biological assessments confirmed that MCF-7 cells incubated within HECS hydrogels preferred to grow into three-dimensional spheroids. Importantly, the cells displayed enhanced migrative capability and upregulated expression levels of MMP-2, TGF-β and VEGF in comparison to two-dimension cultured cells. Hence, the HECS hydrogels show great promise as a biomimetic ECM in constructing breast tumor models.

Keywords: 3D tumor model; Hydrogel; Hydroxyethyl chitosan.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chitosan / chemistry*
  • Extracellular Matrix / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hyaluronic Acid / chemistry*
  • Hydrogels / chemical synthesis*
  • Hydrogels / chemistry
  • Hydrogels / pharmacology
  • MCF-7 Cells
  • Matrix Metalloproteinase 2 / metabolism
  • Porosity
  • Schiff Bases
  • Spheroids, Cellular / cytology*
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Transforming Growth Factor beta / metabolism
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Hydrogels
  • Schiff Bases
  • Transforming Growth Factor beta
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Hyaluronic Acid
  • Chitosan
  • MMP2 protein, human
  • Matrix Metalloproteinase 2