Single-cell RNA-seq analysis of cancer-endothelial cell interactions in primary tumor and peritoneal metastasis from a single patient with colorectal cancer
- Yuri Sakimoto 1,2, Kohei Kumegawa 3, Shimpei Matsui 1,4, Tomohiro Yamaguchi 4, Toshiki Mukai 4, Koji Okabayashi 1, Seiichi Mori 5, Yuko Kitagawa 1, Takashi Akiyoshi 4, Reo Maruyama 6,7
- Yuri Sakimoto 1,2, Kohei Kumegawa 3, Shimpei Matsui 1,4
- 1Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
- 2Project for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
- 3Cancer Cell Diversity Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo, Japan.
- 4Department of Colorectal Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
- 5Project for Development of Innovative Research on Cancer Therapeutics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
- 6Project for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. reo.maruyama@jfcr.or.jp.
- 7Cancer Cell Diversity Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo, Japan. reo.maruyama@jfcr.or.jp.
- 0Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
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View abstract on PubMed
Summary
This summary is machine-generated.Colorectal cancer (CRC) peritoneal metastasis involves distinct cancer cell changes and altered interactions with endothelial cells, potentially reducing VEGF dependence and impacting immune infiltration. Further research is needed to validate these findings.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Research
Background
- Peritoneal metastasis is a severe complication of colorectal cancer (CRC).
- Intratumor heterogeneity and tumor microenvironment interactions in CRC peritoneal metastasis are poorly understood.
- Existing research lacks detailed characterization of cellular interactions in this context.
Purpose Of The Study
- To investigate intratumor heterogeneity and cell-cell communication in colorectal cancer peritoneal metastasis.
- To compare molecular features of primary tumors and peritoneal metastases at the single-cell level.
- To identify novel interactions between cancer cells and endothelial cells in peritoneal metastasis.
Main Methods
- Single-cell transcriptome analysis of matched primary CRC tumor and peritoneal metastasis samples.
- Comparative analysis of gene expression profiles between primary and metastatic sites.
- In-depth analysis of cell-cell communication pathways.
Main Results
- Primary tumors showed enrichment of tip endothelial cells involved in angiogenesis.
- Peritoneal metastases lacked tip endothelial cells and exhibited distinct cancer cell signatures related to epithelial-mesenchymal transition and invasiveness.
- Decreased VEGF signaling and increased CXCL-ACKR1 interactions were observed between endothelial and tumor cells in peritoneal metastasis.
Conclusions
- Alterations in cancer-endothelial cell interactions may reduce VEGF signaling dependence in CRC peritoneal metastasis.
- These interactions could influence immune cell infiltration in the metastatic microenvironment.
- Findings require further validation due to the N-of-1 study design.
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