1. Academic Validation
  2. A novel 4D cell culture mimicking stomach peristalsis altered gastric cancer spheroids growth and malignance

A novel 4D cell culture mimicking stomach peristalsis altered gastric cancer spheroids growth and malignance

  • Biofabrication. 2021 Apr 26;13(3). doi: 10.1088/1758-5090/abf6bf.
Juzhi Zhao 1 Ruiqi Wang 1 Jinyu Zhang 1 Yufang Zhao 1 Shupei Qiao 1 Thomas Crouzier 2 3 4 Hongji Yan 2 3 4 Weiming Tian 1
Affiliations

Affiliations

  • 1 School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, People's Republic of China.
  • 2 Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH, Royal Institute of Technology, AlbaNova University Center, 106 91 Stockholm, Sweden.
  • 3 AIMES-Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden.
  • 4 Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Abstract

In vitroCancer models that can largely mimic thein vivomicroenvironment are crucial for conducting more accurate research. Models of three-dimensional (3D) culture that can mimic some aspects of Cancer microenvironment or Cancer biopsies that can adequately represent tumor heterogeneity are intensely used currently. Those models still lack the dynamic stress stimuli in gastric carcinoma exposed to stomach peristalsisin vivo. This study leveraged a lab-developed four-dimensional (4D) culture model by a magnetic responsive alginate-based hydrogel to rotating magnets that can mimic stress stimuli in gastric Cancer (GC). We used the 4D model to culture human GC cell line AGS and SGC7901, cells at the primary and metastasis stage. We revealed the 4D model altered the Cancer cell growth kinetics mechanistically by alteringPCNAandp53expression compared to the 3D culture that lacks stress stimuli. We found the 4D model altered the Cancer spheroids stemness as evidenced by enhanced Cancer Stem Cells (CD44) marker expression in AGS spheroids but the expression was dampened in SGC7901 cells. We examined the multi-drug resistance (MDR1) marker expression and found the 4D model dampened the MDR1 expression in SGC7901 cell spheroids, but not in spheroids of AGS cells. Such a model provides the stomach peristalsis mimic and is promising for conducting basic or translational GC-associated research, drug screening, and culturing patient gastric biopsies to tailor the therapeutic strategies in precision medicine.

Keywords

alginate; gastric cancer spheroids; magnetic hydrogel; stress stimuli.

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