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Establishment of a novel microfluidic co-culture system for simultaneous analysis of multiple indicators of gefitinib
Xin Li1, Wanming Li1, Jie Wang1
1Department of Cell Biology, Key Laboratory of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, Ministry of Public Health, China Medical University, Shenyang, 110122, PR China.
Mikrochimica Acta
|April 22, 2024
Summary
Cancer-associated fibroblasts (CAFs) reduce colorectal cancer (CRC) cell sensitivity to gefitinib by promoting proliferation and invasion via exosomes. Targeting CAFs or exosomes may enhance CRC treatment efficacy.
Area of Science:
- Oncology
- Biotechnology
- Cancer Biology
Background:
- The therapeutic efficacy of gefitinib in colorectal cancer (CRC) remains uncertain.
- Tumor microenvironment stromal cells, such as cancer-associated fibroblasts (CAFs), may influence drug sensitivity in CRC.
Purpose of the Study:
- To investigate the impact of CAFs on CRC cell sensitivity to gefitinib using a novel microfluidic co-culture system.
- To explore the mechanisms by which CAFs affect CRC cell response to gefitinib.
Main Methods:
- Development of a microfluidic co-culture system enabling long-term cell survival and invasion studies.
- Simultaneous evaluation of CRC cell proliferation and invasiveness.
- Real-time monitoring of dynamic drug response and individual cell trajectories using a live cell workstation.
- Analysis of epithelial-mesenchymal transition (EMT) markers via immunofluorescence and western blot assays.
Main Results:
- Co-culture with CAFs promoted CRC cell proliferation and invasion.
- CAFs reduced CRC cell sensitivity to gefitinib, mediated by secreted exosomes.
- CAF-induced EMT was identified as a mechanism affecting gefitinib response.
- CAFs altered multiple biological characteristics of CRC cells within the tumor microenvironment.
Conclusions:
- CAFs significantly impact CRC cell behavior and gefitinib sensitivity through exosome secretion and EMT induction.
- Targeting CAFs or their secreted exosomes presents a potential strategy to overcome gefitinib resistance in CRC.
- The developed microfluidic system serves as a valuable platform for studying tumor microenvironment interactions and drug resistance mechanisms.
