(A) study on phenotype change of gastric fibroblasts by 3D cell culture matrix and gastric cancer cell secretome

Abstract

Cancer-associated fibroblasts (CAFs) are non-epithelial stromal cells present in the tumor microenvironment (TME) and are known to be involved in the entire stages of cancer and affect cancer progression. CAFs have long been considered as a homogenous population, but recent advances in technologies such as single cell sequencing have revealed that CAFs have heterogeneity, and each subpopulation exhibit distinct phenotypes and functions. The heterogeneity of CAFs affects the patient's prognosis and drug response. Despite the importance of such CAFs heterogeneity, the relationship between certain niche factors and CAFs subtype has not been studied yet. In this study, four different molecular subtypes of fibroblasts are induced through cell culture matrices (collagen and tissue-specific ECM) and gastric cancer cell secretome, and molecular characteristics of each subtype were further analyzed. According to cell embedding matrix, fibroblasts in collagen and tissue-specific ECM acquired myofibroblast-like and inflammatory fibroblast-like features each. By addition of cancer cell secretome, cytokine secretion-related genes were more enhanced in both matrices. These engineered fibroblasts can be used for in vitro tumor models that reflect the fibroblast heterogeneity.