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Updated: Jun 9, 2025
High-sensitivity Detection of Micrometastases Generated by GFP Lentivirus-transduced Organoids Cultured from a Patient-derived Colon Tumor
Published on: June 14, 2018
Effects of simulated microgravity on colorectal cancer organoids growth and drug response
Soon-Chan Kim1,2,3, Min Jung Kim2,4,5, Ji Won Park2,4,5
1Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
Abstract:
Cellular and molecular dynamics of human cells are constantly affected by gravity. Alteration of the gravitational force disturbs the cellular equilibrium, which might modify physiological and molecular characteristics. Nevertheless, biological responses of cancer cells to reduced gravitational force remains obscure. Here, we aimed to comprehend not only transcriptomic patterns but drug responses of colorectal cancer (CRC) under simulated microgravity. We established four organoids directly from CRC patients, and organoids cultured in 3D clinostat were subjected to genome wide expression profiling and drug library screening. Our observations revealed changes in cell morphology and an increase in cell viability under simulated microgravity compared to their static controls. Transcriptomic analysis highlighted a significant dysregulation in the TBC1D3 family of genes. The upregulation of cell proliferation observed under simulated microgravity conditions was further supported by enriched cell cycle processes, as evidenced by the functional clustering of mRNA expressions using cancer hallmark and gene ontology terms. Our drug screening results indicated an enhanced response rate to 5-FU under conditions of simulated microgravity, suggesting potential implications for cancer treatment strategies in simulated microgravity.
Insights
Simulated microgravity alters colorectal cancer (CRC) cell behavior, increasing viability and proliferation. This environment enhances the effectiveness of 5-fluorouracil (5-FU) chemotherapy for CRC treatment.
Area of Science:
- Space biology
- Oncology
- Genomics
Background:
- Gravity influences human cell dynamics, but cancer cell responses to microgravity are not well understood.
- Understanding these responses is crucial for potential space-based cancer research and treatment.
Purpose of the Study:
- To investigate the transcriptomic and drug response profiles of colorectal cancer (CRC) organoids under simulated microgravity.
- To identify molecular and physiological changes in CRC cells exposed to reduced gravitational forces.
Main Methods:
- Established four patient-derived colorectal cancer organoids.
- Utilized a 3D clinostat to simulate microgravity.
- Performed genome-wide expression profiling and drug library screening.
Main Results:
- Simulated microgravity increased CRC cell viability and altered cell morphology.
- Transcriptomic analysis revealed significant dysregulation in the TBC1D3 gene family.
- Enriched cell cycle processes indicated upregulated cell proliferation.
- Enhanced response rates to 5-fluorouracil (5-FU) were observed under simulated microgravity.
Conclusions:
- Simulated microgravity significantly impacts CRC cell behavior, promoting proliferation and altering gene expression.
- The enhanced sensitivity to 5-FU suggests potential therapeutic strategies for colorectal cancer in microgravity environments.
