Research Paper Volume 15, Issue 5 pp 1652—1667
ANGPTL2 promotes VEGF-A synthesis in human lung cancer and facilitates lymphangiogenesis
- 1 Department of General Thoracic Surgery, Asia University Hospital, Taichung, Taiwan
- 2 Department of Physical Therapy, Asia University, Taichung, Taiwan
- 3 Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
- 4 Translational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- 5 Division of General Thoracic Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
- 6 Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
- 7 Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan
- 8 Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan
- 9 Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- 10 School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
- 11 Institute of Biomedical Sciences, Mackay Medical College, Taipei, Taiwan
- 12 School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
- 13 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
- 14 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
- 15 Department of Medical Laboratory Science and Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
- 16 Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
Received: December 20, 2022 Accepted: March 1, 2023 Published: March 13, 2023
https://doi.org/10.18632/aging.204581How to Cite
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.