Li JJ, Mao JX, Zhong HX, Zhao YY, Teng F, Lu XY, Zhu LY, Gao Y, Fu H, Guo WY. Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review. World J Hepatol 2024; 16(4): 537-549 [PMID: 38689749 DOI: 10.4254/wjh.v16.i4.537]
Corresponding Author of This Article
Wen-Yuan Guo, MD, Adjunct Professor, Department of Liver Surgery and Organ Transplantation, Shanghai Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai 200003, China. guowenyuan@smmu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Apr 27, 2024; 16(4): 537-549 Published online Apr 27, 2024. doi: 10.4254/wjh.v16.i4.537
Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review
Jing-Jing Li, Jia-Xi Mao, Han-Xiang Zhong, Yuan-Yu Zhao, Fei Teng, Xin-Yi Lu, Li-Ye Zhu, Yang Gao, Hong Fu, Wen-Yuan Guo
Jing-Jing Li, Jia-Xi Mao, Han-Xiang Zhong, Yuan-Yu Zhao, Fei Teng, Xin-Yi Lu, Li-Ye Zhu, Yang Gao, Hong Fu, Wen-Yuan Guo, Department of Liver Surgery and Organ Transplantation, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200003, China
Co-first authors: Jing-Jing Li and Jia-Xi Mao.
Co-corresponding authors: Wen-Yuan Guo and Fei Teng.
Author contributions: Li JJ and Mao JX contributed equally to this work as co-first authors, and were responsibility for designing and writing the manuscript; Guo WY and Teng F acted as co-corresponding authors who contributed equally to this work, and participated in revising and finalizing the manuscript; Zhao YY, Lu XY and Gao Y prepared the figures; Fu H and Zhu LY provided data support.
Supported byNational Natural Science Foundation of China, No. 81702923, and No. 81971503; Open Project of State Key Laboratory of Medical Immunology, No. NKLMI2023K03; Shanghai Shen Kang Hospital Development Center Clinical Science and Technology Innovation Project, No. SHDC12020104; and Basic Medical Research Project of Naval Medical University, No. 2022QN072.
Conflict-of-interest statement: The authors declared that there is no conflict of interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wen-Yuan Guo, MD, Adjunct Professor, Department of Liver Surgery and Organ Transplantation, Shanghai Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai 200003, China. guowenyuan@smmu.edu.cn
Received: December 10, 2023 Peer-review started: December 10, 2023 First decision: December 15, 2023 Revised: January 11, 2024 Accepted: March 18, 2024 Article in press: March 18, 2024 Published online: April 27, 2024 Processing time: 136 Days and 1.8 Hours
Abstract
The tumor microenvironment is a complex network of cells, extracellular matrix, and signaling molecules that plays a critical role in tumor progression and metastasis. Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits. However, recent studies have shown that lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) also play multifaceted roles in the tumor microenvironment beyond their structural functions, particularly in hepatocellular carcinoma (HCC). This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC, including their involvement in angiogenesis, immune modulation, lymphangiogenesis, and metastasis. By providing a detailed account of the complex interplay between LECs, BECs, and tumor cells, this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.
Core Tip: Lymphatic and blood endothelial cells are important components of stromal cells in the tumor microenvironment. Besides their essential function in the formation of tumor draining blood and lymphatic vessels, they can activate various signaling pathways to promote tumor development and metastasis. This review discusses lymphangiogenesis and angiogenesis, and summarizes the current knowledge on common markers of lymphatic and blood endothelial cells and their roles in tumor metastasis, particularly in hepatocellular carcinoma. Based on the available evidence, researchers are attempting to discover new targeted therapies for the prevention of tumor progression.
