posted on 2023-06-24, 04:29authored byHongren Yao, Yuxuan Li, Yajing Zheng, Jin-Ming Lin
Tumor–stroma interaction is the core process of
tumor metastasis.
Therefore, building a model of tumor–stromal cell communication
is crucial for understanding the tumor metastasis process and curing
cancer completely. In this research, a controllable three-dimensional
(3D) tumor–stroma coculture microsphere model based on droplet
microfluidic technology was developed to culture human lung cancer
cells (A549 cell) and fibroblast cells (NIH-3T3 cell) using core–shell
hydrogel microspheres to partition different kinds of cells. In our
coculture model, tumor cells show a trend of epithelial–mesenchymal
transition (EMT): a decrease in the number of surface E-cadherin and
an increase in the number of N-cadherin. At the same time, fibroblasts
are activated into cancer-associated fibroblasts (CAFs) as the level
of interleukin-6 (IL-6) released is increased. In addition, an interesting
phenomenon was discovered; in the absence of fibroblasts, the metabolism
of the tumor cell culture alone leads to arginine depletion and citrulline
accumulation, whereas a coculture can maintain the arginine–ornithine–citrulline
cycle to reach equilibrium after 72 h, and the balance increases the
stress resistance of tumor cells. This discovery may provide a new
direction for understanding tumor resistance.