Research Paper Volume 12, Issue 21 pp 21837—21853
Galectin-1 promotes vasculogenic mimicry in gastric adenocarcinoma via the Hedgehog/GLI signaling pathway
- 1 Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University (Taizhou People’s Hospital) Taizhou, Jiangsu Province, China
Received: February 23, 2020 Accepted: July 29, 2020 Published: November 10, 2020https://doi.org/10.18632/aging.104000
How to Cite
Copyright: © 2020 You 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.
Background: Galectin-1 (GAL-1), which is encoded by LGALS1, promotes vasculogenic mimicry (VM) in gastric cancer (GC) tissue. However, the underlying mechanism remains unclear.
Methods: Immunohistochemical (IHC) and CD34-periodic acid-Schiff (PAS) double staining were used to investigate Glioma-associated oncogene-1(GLI1) expression and VM in paraffin-embedded sections from 127 patients with GC of all tumor stages. LGALS1 or GLI1 were stably transduced into MGC-803 cells and AGS cells, and western blotting, IHC, CD34-PAS double staining and three-dimensional culture in vitro, and tumorigenicity in vivo were used to explore the mechanisms of GAL-1/ GLI1 promotion of VM formation in GC tissues.
Results: A significant association between GAL-1 and GLI1 expression was identified by IHC staining, as well as a significant association between GLI1 expression and VM formation. Furthermore, overexpression of LGALS1 enhanced expression of GLI1 in MGC-803 and AGS cells. GLI1 promoted VM formation both in vitro and in vivo. The effects of GLI1 on VM formation were independent of LGALS1. Importantly, the expression of VM-related molecules, such as MMP2, MMP14 and laminin5γ2, was also affected upon GLI1 overexpression or silencing in GC cell lines. Conclusion: GAL-1 promotes VM in GC through the Hh/GLI pathway, which has potential as a novel therapeutic target for treatment of VM in GC.
DMSO: Dimethyl sulfoxide; FBS: Fetal bovine serum; GAL-1: Galectin-1; GC: Gastric cancer; H&E: Hematoxylin and eosin; HRP: Horseradish peroxidase; IHC: Immunohistochemical;; OE: Overexpressing; PAS: Periodic acid-Schiff; PKA: Protein kinase A; qRT-PCR: Quantitative reverse transcription-PCR; Smo: Smoothened; SDS-PAGE: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SHh: Sonic Hedgehog; VEGFR: Vascular endothelial growth factor receptor; VM: Vasculogenic mimicry; WC: Wild-type control.