3D in vitro co-culture disc for spatiotemporal image analysis of cancer–stromal cell interaction. (17th May 2021)

• Record Type: Journal Article
• Authors: Takahashi, Haruko; Kikuchi, Yutaka
• Is Part Of: Biomaterials science. Volume 9:Number 12(2021)
• Page Start: 4448
• Page End: 4458
• Publication Date: 2021-05-17
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d1bm00629k
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : A 3D in vitro cancer-stroma co-culture system, a co-culture disc, was developed for the spatiotemporal image analysis of bi-directional communication between cancer cells and surrounding stromal cell in the tumour microenvironment. Abstract : Assessing phenotypic changes in both cancer cells and surrounding cells, which construct the tumour microenvironment, is essential for understanding the role of bi-directional communication among cells in the tumorigenic process. Here, a 3D in vitro cancer-stroma co-culture system, a co-culture disc, was reported for the spatiotemporal image analysis of cancer–stromal cell interactions. Due to their centre-open disc structure, the lung cancer A549 spheroids could be co-cultured with a high concentration of fibroblasts, without gel shrinkage in the long term (>1 month). In the co-culture disc, some populations of applied normal human lung fibroblasts showed morphological and phenotypic changes into activated myofibroblasts (AMFs) with high expression of myo-fibrotic α-smooth muscle actin fibre in the cell, which is a well-known feature of cancer-associated fibroblasts. The AMFs appeared heterogeneously at the boundary of cancer spheroids, which could not be detected by standard mass analysis using a quantitative RT-qPCR system, and they led to A549 cancer cell migration. In addition, the effects of oncogenic or medicinal additives were quantitatively assessed by combining co-culture discs with image analysis. This system provides a new potential technique to analyse the complicated crosstalk among cancer tissue-constructing cells during the tumorigenic process and provides insight into applications for the quantitative evaluation of substances inducing tumorigenesis as well as drugs to prevent and inhibit cancer progression.