Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression.
BACKGROUND
Galectin-1, an evolutionarily conserved glycan-binding protein with angiogenic potential, was recently identified as being overexpressed in cancer-associated fibroblasts (CAFs) of gastric cancer. The role of endogenous CAF-derived galectin-1 on angiogenesis in gastric cancer and the mechanism involved remain unknown.


METHODS
Immunohistochemical staining was used to investigate the correlation between galectin-1 and vascular endothelial growth factor (VEGF) and CD31 expression in gastric cancer tissues and normal gastric tissues. Galectin-1 was knocked down in CAFs isolated from gastric cancer using small interfering ribonucleic acid (RNA), or overexpressed using recombinant lentiviruses, and the CAFs were co-cultured with human umbilical vein endothelial cells (HUVECs) or cancer cells. Subsequently, proliferation, migration, tube formation, and VEGF/VEGF receptor (VEGFR) 2 expression were detected. The role of CAF-derived galectin-1 in tumor angiogenesis in vivo was studied using the chick chorioallantoic membrane (CAM) assay.


RESULTS
Galectin-1 was highly expressed in the CAFs and was positively associated with VEGF and CD31 expression. In the co-culture, high expression of galectin-1 in the CAFs increased HUVEC proliferation, migration, tube formation, and VEGFR2 phosphorylation and enhanced VEGF expression in gastric cancer cells. The CAM assay indicated that high expression of galectin-1 in the CAFs accelerated tumor growth and promoted angiogenesis. In contrast, galectin-1 knockdown in the CAFs significantly inhibited this effect.


CONCLUSIONS
CAF-derived galectin-1 significantly promotes angiogenesis in gastric cancer and may be a target for angiostatic therapy.
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China.
Dong
D
Tang
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China.
Jun
J
Gao
College of Clinical Medicine, Nanjing Medical University (the First Affiliated Hospital of Nanjing Medical University), Nanjing, 211166, People's Republic of China.
Sen
S
Wang
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China.
Nianyuan
N
Ye
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China.
Yang
Y
Chong
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China.
Yuqin
Y
Huang
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China.
Jie
J
Wang
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China.
Bin
B
Li
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China.
Wei
W
Yin
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China. daorong666@sina.com.
Daorong
D
Wang
D000328:Adult; D000368:Aged; D000818:Animals; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000378:metabolism; D018920:Coculture Techniques / Q000379:methods; D005260:Female; D037483:Galectin 1 / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D037483:Galectin 1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
Angiogenesis; Cancer-associated fibroblasts; Galectin-1; Gastric cancer