Up-regulation of extracellular matrix in 5-FU resistant Hela
carcinoma cells
ECM, a complex network which is composed of a variety of macromolecules
surrounding cells, provides cells with spatial structure and physical
support, mediates multiple signal pathways, and plays an important role
in cancer progression, invasion and metastasis, and drug resistance
(Langhans, 2018). Integrin could
be involved in CAM-DR by binding to ECM (e.g., collagen I) and activate
drug efflux of ABC transporters to develop drug resistance (Baltes et
al., 2020).It was found that ECM participated in the regulation of cell
cycle by stimulating integrin mediated PI3K activation to protect small
cell lung cancer from damages caused by radiotherapy and chemotherapy
(Hodkinson et al., 2007). Consistent with these findings, we found in
this study the expression of ECM including laminin and collagen was
increased in the 3D MTSs (Figure. 4 and Figure. 5A-D ),
meanwhile the molecular function of integrin binding was also increased
in the 3D MTSs (Table S3 and Table S4 ), including
up-regulation of ITGB1 and ITGA5 on the mRNA and protein level,
respectively (Figure. 5A ). These significance difference
between 2D monolayer and 3D MTSs may contribute to the increase of
resistance to 5-FU. Therefore, ECM would become a potential target for
improving the effect of anticancer therapy.