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Genome-wide RNA-Seq identifies TP53-mediated embryonic stem cells inhibiting tumor invasion and metastasis
Yatong Li1,2, Yongna Fan3, Yunyi Xie3
1Department of Radiology, Peking Union Medical College Hospital, Beijing, 100730, China. yatongli@qq.com.
Abstract:
The discovery of embryonic stem cell (ESC) mediating tumoricidal activity revealed the intimate relationship between ESCs and tumor cells, but the functional role of ESCs in tumor progression is poorly understood. To further investigate tumor cell and ESC interactions, we co-cultured mouse ESCs with mouse pancreatic cancer Pan02 cells or mouse melanoma B16-F10 cells in Transwell, and found that tumor cell invasion was significantly inhibited by ESCs. Application of ESCs to tumor-bearing mice resulted in significant inhibition of tumor metastasis in vivo. RNA-Seq analyses of tumor cell and ESC co-cultures identified TP53 and related signalling as major pathways involved in ESC-mediated inhibition of tumor cell invasion and metastasis, which indicated the potential clinical application of ESCs to treat cancer.
Insights
Embryonic stem cells (ESCs) can inhibit tumor cell invasion and metastasis. This study reveals TP53 signaling as a key pathway, suggesting ESCs as a potential cancer therapy.
Area of Science:
- Cancer Biology
- Stem Cell Research
- Tumor Microenvironment
Background:
- Embryonic stem cells (ESCs) exhibit tumoricidal activity, but their role in tumor progression remains unclear.
- Understanding the interaction between ESCs and tumor cells is crucial for developing novel cancer therapies.
Purpose of the Study:
- To investigate the functional role of ESCs in inhibiting tumor cell invasion and metastasis.
- To identify the molecular pathways involved in ESC-mediated anti-tumor effects.
Main Methods:
- Co-culture of mouse ESCs with mouse pancreatic cancer (Pan02) and melanoma (B16-F10) cells using Transwell assays.
- In vivo studies involving the application of ESCs to tumor-bearing mice.
- RNA-sequencing (RNA-Seq) analysis of co-cultured cells to identify involved signaling pathways.
Main Results:
- ESCs significantly inhibited tumor cell invasion in vitro.
- In vivo administration of ESCs resulted in a significant reduction in tumor metastasis.
- RNA-Seq analysis identified TP53 and related signaling pathways as critical mediators of ESC-induced anti-tumor effects.
Conclusions:
- Embryonic stem cells possess potent capabilities to inhibit cancer cell invasion and metastasis.
- TP53 signaling is a key pathway through which ESCs exert their anti-cancer effects.
- ESCs represent a promising therapeutic strategy for cancer treatment.
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