Research Paper|Volume 15, Issue 5|pp 1652—1667

ANGPTL2 promotes VEGF-A synthesis in human lung cancer and facilitates lymphangiogenesis

Po-I Liu^1,², Ya-Jing Jiang³, An-Chen Chang⁴, Chang-Lun Huang^3,⁵, Yi-Chin Fong^6,⁷, Jeng-Hung Guo^3,⁸, Chun-Lin Liu^3,⁸, Shih-Wei Wang^9,^10,¹¹, Ju-Fang Liu¹², Sunny Li-Yu Chang³, Chih-Hsin Tang^3,^13,^14,^15,¹⁶

¹Department of General Thoracic Surgery, Asia University Hospital, Taichung, Taiwan
²Department of Physical Therapy, Asia University, Taichung, Taiwan
³Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
⁴Translational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
⁵Division of General Thoracic Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
⁶Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
⁷Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan
⁸Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan
⁹Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
¹⁰School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
¹¹Institute of Biomedical Sciences, Mackay Medical College, Taipei, Taiwan
¹²School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
¹³Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
¹⁴Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
¹⁵Department of Medical Laboratory Science and Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
¹⁶Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan

* Joint first author

Received: December 20, 2022Accepted: March 1, 2023Published: March 13, 2023

https://doi.org/10.18632/aging.204581

Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Lung cancer is an extremely common cancer and metastatic lung cancer has a greatly low survival rate. Lymphangiogenesis is essential for the development and metastasis of lung cancer. The adipokine angiopoietin-like protein 2 (ANGPTL2) regulates tumor progression and metastasis, although the functions of ANGPTL2 in lung cancer are unknown. Analysis of data from TCGA genomics program, the GEPIA web server and the Oncomine database revealed that higher levels of ANGPTL2 expression were correlated with progressive disease and lymph node metastasis. ANGPTL2 enhanced VEGF-A-dependent lymphatic endothelial cell (LEC) tube formation and migration. Integrin α5β1, p38 and nuclear factor (NF)-κB signaling mediated ANGPTL2-regulated lymphangiogenesis. Importantly, overexpression ANGPTL2 facilitated tumor growth and lymphangiogenesis in vivo. Thus, ANGPTL2 is a promising therapeutic object for treating lung cancer.