Endothelial cell heterogeneity in colorectal cancer: tip cells drive angiogenesis.

Autor: Xie Z; Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 Changle Road, Xi'an, Shaanxi, 710032, China., Niu L; Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 Changle Road, Xi'an, Shaanxi, 710032, China., Du K; Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 Changle Road, Xi'an, Shaanxi, 710032, China., Chen L; Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China., Zheng G; Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 Changle Road, Xi'an, Shaanxi, 710032, China., Dai S; Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, 110016, China.; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, 110016, China., Dan H; Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 Changle Road, Xi'an, Shaanxi, 710032, China., Duan L; Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 Changle Road, Xi'an, Shaanxi, 710032, China., Dou X; Xi'an Medical University, Xi'an, Shaanxi, 710021, China., Feng F; Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 Changle Road, Xi'an, Shaanxi, 710032, China. surgeonfengfan@163.com., Zhang J; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, 169 Changle Road, Xi'an, Shaanxi, 710032, China. biozhangj@fmmu.edu.cn., Zheng J; Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 169 Changle Road, Xi'an, Shaanxi, 710032, China. zhjy68@163.com.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Aug 22; Vol. 81 (1), pp. 365. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1007/s00018-024-05411-z
Abstrakt: This study aims to uncover the heterogeneity of endothelial cells (ECs) in colorectal cancer (CRC) and their crucial role in angiogenesis, with a special focus on tip cells. Using single-cell RNA sequencing to profile ECs, our data suggests that CRC ECs predominantly exhibit enhanced angiogenesis and decreased antigen presentation, a shift in phenotype largely steered by tip cells. We also observed that an increase in the density and proportion of tip cells correlates with CRC occurrence, progression, and poorer patient prognosis. Furthermore, we identified endothelial cell-specific molecule 1 (ESM1), specifically expressed in tip cells, sustains a VEGFA-KDR-ESM1 positive feedback loop, promoting angiogenesis and CRC proliferation and migration. We also found the enrichment of KDR in tip cells and spotlight a unique long-tail effect in VEGFA expression: while VEGFA is primarily expressed by epithelial cells, the highest level of VEGFA expression is found in individual myeloid cells. Moreover, we observed that effective PD-1 blockade immunotherapy significantly reduced tip cells, disrupting the VEGFA-KDR-ESM1 positive feedback loop in the process. Our investigation into the heterogeneity of ECs in CRC at a single-cell level offers important insights that may contribute to the development of more effective immunotherapies targeting tip cells in CRC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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