Enhancement of Tumorigenicity, Spheroid Niche, and Drug Resistance of Pancreatic Cancer Cells in Three-Dimensional Culture System

Hao-Chien Hung; Tsui-Lien Mao; Ming-Huei Fan; Guan-Zhi Huang; Ainani Priza Minhalina; Chi-Long Chen; Chao-Lien Liu

doi:10.7150/jca.87494

Enhancement of Tumorigenicity, Spheroid Niche, and Drug Resistance of Pancreatic Cancer Cells in Three-Dimensional Culture System

J Cancer. 2024 Mar 2;15(8):2292-2305. doi: 10.7150/jca.87494. eCollection 2024.

Authors

Hao-Chien Hung¹, Tsui-Lien Mao^{2

3}, Ming-Huei Fan⁴, Guan-Zhi Huang⁴, Ainani Priza Minhalina⁴, Chi-Long Chen^{5

6}, Chao-Lien Liu^{4

7}

Affiliations

¹ Department of General Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan.
² Department of Pathology, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
³ Department of Pathology, National Taiwan University Hospital, Taipei 10002, Taiwan.
⁴ School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
⁵ Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
⁶ Department of Pathology, Taipei Medical University Hospital, Taipei 11031, Taiwan.
⁷ PhD Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

Abstract

The three-dimensional (3D) cell culture technique has been applied comprehensively as a variable platform for medical research, biochemical signal pathway analysis, and evaluation of anti-tumor treatment response due to an excellent recapitulation of a tumor microenvironment (TME) in the in vitro cultured cancer cells. Pancreatic cancer (PaC) is one of the toughest malignancies with a complex TME and refractory treatment response. To comprehensively study the TME of PaC, there is an eager need to develop a 3D culture model to decompose the cellular components and their cross interactions. Herein, we establish a 3D PaC culture system with cancer stem cell (CSC) and scalability properties. To validate our model, we tested the individual PaC cell and the combined effects with cancer-associated fibroblasts (CAFs) on cancer tumorigenicity, the cellular interaction through the CXCR3/CXCL10 axis, and cellular responses reflection of anti-cancer treatments. With the help of our 3D technology, a simulated malignant spheroid with important stromal populations and TME physiochemical properties may be successfully recreated. It can be used in a wide range of preclinical research and helpful in advancing basic and translational cancer biology.

Keywords: CXCR3/CXCL10 axis; Pancreatic cancer (PaC); cancer-associated fibroblast (CAF); spheroid model; therapeutic discovery.; three dimensional (3D); two dimensional (2D).