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Updated: Aug 13, 2025
Isolation and Culture Expansion of Tumor-specific Endothelial Cells
Published on: October 14, 2015
Single-cell analysis of multiple cancer types reveals differences in endothelial cells between tumors and normal
Jiayu Zhang1, Tong Lu1, Shiqi Lu2
1Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China.
Abstract:
Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor (VEGF) pathway. Some patients do benefit from anti-VEGF/VEGFR therapy; however, a large number of patients do not have response or acquire drug resistance after treatment. Moreover, anti-VEGF/VEGFR therapy may lead to nephrotoxicity and cardiovascular-related side effects due to its action on normal ECs. Therefore, it is necessary to identify targets that are specific to tumor ECs and could be applied to various cancer types. We integrated single-cell RNA sequencing data from six cancer types and constructed a multi-cancer EC atlas to decode the characteristic of tumor ECs. We found that tip-like ECs mainly exist in tumor tissues but barely exist in normal tissues. Tip-like ECs are involved in the promotion of tumor angiogenesis and inhibition on anti-tumor immune responses. Moreover, tumor cells, myeloid cells, and pericytes are the main sources of pro-angiogenic factors. High proportion of tip-like ECs is associated with poor prognosis in multiple cancer types. We also identified that prostate-specific membrane antigen (PSMA) is a specific marker for tip-like ECs in all the cancer types we studied. In summary, we demonstrate that tip-like ECs are the main differential EC subcluster between tumors and normal tissues. Tip-like ECs may promote tumor progression through promoting angiogenesis while inhibiting anti-tumor immune responses. PSMA was a specific marker for tip-like ECs, which could be used as a potential target for the diagnosis and treatment of non-prostate cancers.
Insights
Researchers identified tip-like endothelial cells (ECs) as key drivers of tumor growth and resistance to anti-angiogenic therapies. Prostate-specific membrane antigen (PSMA) emerged as a specific marker for these tumor-associated ECs, offering a potential new therapeutic target.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Endothelial cells (ECs) are crucial in tumor progression, with the vascular endothelial growth factor (VEGF) pathway being a primary target for anti-angiogenic therapies.
- Current anti-VEGF/VEGFR therapies show limited efficacy and can cause side effects due to targeting normal ECs, necessitating the identification of tumor-specific EC targets.
- There is a need for novel therapeutic targets specific to tumor ECs that are effective across various cancer types.
Purpose of the Study:
- To identify and characterize endothelial cell (EC) subtypes specific to tumors across multiple cancer types.
- To investigate the role of these tumor-specific ECs in tumor progression, angiogenesis, and anti-tumor immunity.
- To discover a specific marker for these tumor-associated ECs for potential diagnostic and therapeutic applications.
Main Methods:
- Integration of single-cell RNA sequencing data from six distinct cancer types to create a comprehensive multi-cancer EC atlas.
- Comparative analysis of EC populations in tumor tissues versus normal tissues to identify differential cell clusters.
- Identification and validation of specific molecular markers associated with tumor-enriched EC subtypes.
Main Results:
- Tip-like ECs were found to be significantly enriched in tumor tissues compared to normal tissues, distinguishing them as a key tumor-associated EC subcluster.
- These tip-like ECs were implicated in promoting tumor angiogenesis and suppressing anti-tumor immune responses.
- High proportions of tip-like ECs correlated with poor prognosis across multiple cancer types.
- Prostate-specific membrane antigen (PSMA) was identified as a specific marker for tip-like ECs across all studied cancer types.
Conclusions:
- Tip-like ECs represent a distinct endothelial cell subcluster prevalent in tumors and play a significant role in tumor progression by enhancing angiogenesis and hindering anti-tumor immunity.
- PSMA serves as a specific marker for these tumor-associated tip-like ECs, presenting a promising target for the diagnosis and treatment of various cancers, including non-prostate malignancies.
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