B7-H3 promotes colorectal cancer angiogenesis through activating the NF-κB pathway to induce VEGFA expression.
Animals
B7 Antigens
/ metabolism
Cell Line, Tumor
Cell Movement
Collagen
Colorectal Neoplasms
/ blood supply
Drug Combinations
Female
Human Umbilical Vein Endothelial Cells
/ metabolism
Humans
Laminin
Mice, Inbred BALB C
Mice, Nude
Microvessels
/ pathology
NF-kappa B
/ metabolism
Neoplasm Invasiveness
Neovascularization, Pathologic
/ metabolism
Proteoglycans
Signal Transduction
Vascular Endothelial Growth Factor A
/ metabolism
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
23 01 2020
23 01 2020
Historique:
received:
06
09
2019
accepted:
10
01
2020
revised:
09
01
2020
entrez:
25
1
2020
pubmed:
25
1
2020
medline:
15
1
2021
Statut:
epublish
Résumé
Tumor angiogenesis is a hallmark of cancer and is involved in the tumorigenesis of solid tumors. B7-H3, an immune checkpoint molecule, plays critical roles in proliferation, metastasis and tumorigenesis in diverse tumors; however, little is known about the biological functions and molecular mechanism underlying B7-H3 in regulating colorectal cancer (CRC) angiogenesis. In this study, we first demonstrated that the expression of B7-H3 was significantly upregulated and was positively associated with platelet endothelial cell adhesion molecule-1 (CD31) level in tissue samples from patients with CRC. In addition, a series of in vitro and in vivo experiments showed that conditioned medium from B7-H3 knockdown CRC cells significantly inhibited the migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs), whereas overexpression of B7-H3 had the opposite effect. Furthermore, B7-H3 promoted tumor angiogenesis by upregulating VEGFA expression. Recombinant VEGFA abolished the inhibitory effects of conditioned medium from shB7-H3 CRC cells on HUVEC angiogenesis, while VEGFA siRNA or a VEGFA-neutralizing antibody reversed the effects of conditioned medium from B7-H3-overexpressing CRC cells on HUVEC angiogenesis. Moreover, we verified that B7-H3 upregulated VEGFA expression and angiogenesis by activating the NF-κB pathway. Collectively, our findings identify the B7-H3/NF-κB/VEGFA axis in promoting CRC angiogenesis, which serves as a promising approach for CRC treatment.
Identifiants
pubmed: 31974361
doi: 10.1038/s41419-020-2252-3
pii: 10.1038/s41419-020-2252-3
pmc: PMC6978425
doi:
Substances chimiques
B7 Antigens
0
CD276 protein, human
0
Drug Combinations
0
Laminin
0
NF-kappa B
0
Proteoglycans
0
Vascular Endothelial Growth Factor A
0
matrigel
119978-18-6
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
55Références
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