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Updated: Jun 11, 2025
Isolation and Culture Expansion of Tumor-specific Endothelial Cells
Published on: October 14, 2015
Pan-cancer integrative analyses dissect the remodeling of endothelial cells in human cancers
Jinhu Li1, Dongfang Wang1, Fei Tang1,2
1Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
Abstract:
Therapeutics targeting tumor endothelial cells (TECs) have been explored for decades, with only suboptimal efficacy achieved, partly due to an insufficient understanding of the TEC heterogeneity across cancer patients. We integrated single-cell RNA-seq data of 575 cancer patients from 19 solid tumor types, comprehensively charting the TEC phenotypic diversities. Our analyses uncovered underappreciated compositional and functional heterogeneity in TECs from a pan-cancer perspective. Two subsets, CXCR4 + tip cells and SELE + veins, represented the prominent angiogenic and proinflammatory phenotypes of TECs, respectively. They exhibited distinct spatial organization patterns, and compared to adjacent non-tumor tissues, tumor tissue showed an increased prevalence of CXCR4 + tip cells, yet with SELE + veins depleted. Such functional and spatial characteristics underlie their differential associations with the response of anti-angiogenic therapies and immunotherapies. Our integrative resources and findings open new avenues to understand and clinically intervene in the tumor vasculature.
Insights
Tumor endothelial cell (TEC) heterogeneity impacts cancer therapy. This study reveals two key TEC subsets, CXCR4+ tip cells and SELE+ veins, with distinct roles in tumor growth and inflammation, guiding new therapeutic strategies.
Area of Science:
- Oncology
- Cancer Biology
- Vascular Biology
Background:
- Therapeutics targeting tumor endothelial cells (TECs) show suboptimal efficacy due to poor understanding of TEC heterogeneity.
- Tumor vasculature plays a critical role in cancer progression and treatment response.
Purpose of the Study:
- To comprehensively chart TEC phenotypic diversity across 19 solid tumor types using single-cell RNA sequencing.
- To identify distinct TEC subsets and their functional and spatial characteristics.
- To investigate the association of TEC phenotypes with anti-angiogenic and immunotherapeutic response.
Main Methods:
- Integration of single-cell RNA sequencing data from 575 cancer patients.
- Pan-cancer analysis of TEC heterogeneity.
- Identification and characterization of distinct TEC subsets (CXCR4+ tip cells, SELE+ veins).
- Analysis of spatial organization and differential prevalence in tumor vs. non-tumor tissues.
Main Results:
- Uncovered significant compositional and functional heterogeneity in TECs across diverse cancer types.
- Identified CXCR4+ tip cells (angiogenic) and SELE+ veins (proinflammatory) as prominent TEC subsets.
- Observed distinct spatial patterns: increased CXCR4+ tip cells and decreased SELE+ veins in tumors compared to adjacent non-tumor tissues.
- Demonstrated differential associations of these TEC subsets with anti-angiogenic therapy and immunotherapy response.
Conclusions:
- TEC heterogeneity is a critical factor influencing therapeutic outcomes in cancer.
- CXCR4+ tip cells and SELE+ veins represent key functional and spatial phenotypes of tumor vasculature.
- Understanding and targeting these specific TEC subsets offers new avenues for improving cancer treatments, including anti-angiogenic therapies and immunotherapies.
Related Concept Videos
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01:24Regulation of Angiogenesis and Blood Supply
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