Prognostic significance of VEGF receptors expression on the tumor cells in skull base chordoma.
Adolescent
Adult
Aged
Antigens, CD34
/ metabolism
Biomarkers, Tumor
/ metabolism
Chordoma
/ metabolism
Female
Fetal Proteins
/ metabolism
Follow-Up Studies
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
/ metabolism
Prognosis
Skull Base Neoplasms
/ metabolism
T-Box Domain Proteins
/ metabolism
Vascular Endothelial Growth Factor Receptor-1
/ metabolism
Vascular Endothelial Growth Factor Receptor-2
/ metabolism
Young Adult
Chordoma
Endothelial cell
Programmed death-ligand 1
Regulatory T-cells
Tumor-associated macrophage
Vascular endothelial growth factor receptor
Journal
Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
23
04
2019
accepted:
16
06
2019
pubmed:
27
6
2019
medline:
7
1
2020
entrez:
27
6
2019
Statut:
ppublish
Résumé
Chordoma is a rare refractory neoplasm that arises from the embryological remnants of the notochord, which is incurable using any multimodality therapy. Vascular endothelial growth factor (VEGF) is a potent activator of angiogenesis that is strongly associated with the tumor-immune microenvironment. These factors have not been elucidated for chordomas. To evaluate the characteristics of vascular and tumor cells in chordoma, we first analyzed the expression of VEGF receptor (VEGFR) 1, VEGFR2, CD34, and Brachyury in a cell line and 54 tumor tissues. Patients with primary skull base chordomas were divided into the following two groups as per the tumor growth rate: patients with slow progression (SP: < 3 mm/year) and those with rapid progression (RP: ≥ 3 mm/year). Thus, the expressions of VEGF-A, VEGFR 1, and VEGFR2 on tumor cells; tumor infiltrative immune cells, including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs); and immune-checkpoint molecules (PD-1/PD-L1) were analyzed with the clinical courses, especially in a comparison between the two groups. In chordomas, both VEGFR1 and VEGFR2 were strongly expressed not only on vascular endothelial cells, but also on tumor cells. The recurrent cases showed significantly higher VEGFR1 expressions on tumor cells than the primary cases. The expression of VEGF-A was significantly higher in RP than that in SP group. The numbers of CD163+ TAMs and Foxp3+ Tregs were higher in RP than that in SP group. Expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to tumor growth in patients with chordomas.
Sections du résumé
BACKGROUND
BACKGROUND
Chordoma is a rare refractory neoplasm that arises from the embryological remnants of the notochord, which is incurable using any multimodality therapy. Vascular endothelial growth factor (VEGF) is a potent activator of angiogenesis that is strongly associated with the tumor-immune microenvironment. These factors have not been elucidated for chordomas.
METHODS
METHODS
To evaluate the characteristics of vascular and tumor cells in chordoma, we first analyzed the expression of VEGF receptor (VEGFR) 1, VEGFR2, CD34, and Brachyury in a cell line and 54 tumor tissues. Patients with primary skull base chordomas were divided into the following two groups as per the tumor growth rate: patients with slow progression (SP: < 3 mm/year) and those with rapid progression (RP: ≥ 3 mm/year). Thus, the expressions of VEGF-A, VEGFR 1, and VEGFR2 on tumor cells; tumor infiltrative immune cells, including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs); and immune-checkpoint molecules (PD-1/PD-L1) were analyzed with the clinical courses, especially in a comparison between the two groups.
RESULTS
RESULTS
In chordomas, both VEGFR1 and VEGFR2 were strongly expressed not only on vascular endothelial cells, but also on tumor cells. The recurrent cases showed significantly higher VEGFR1 expressions on tumor cells than the primary cases. The expression of VEGF-A was significantly higher in RP than that in SP group. The numbers of CD163+ TAMs and Foxp3+ Tregs were higher in RP than that in SP group.
CONCLUSIONS
CONCLUSIONS
Expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to tumor growth in patients with chordomas.
Identifiants
pubmed: 31240525
doi: 10.1007/s11060-019-03221-z
pii: 10.1007/s11060-019-03221-z
doi:
Substances chimiques
Antigens, CD34
0
Biomarkers, Tumor
0
Fetal Proteins
0
T-Box Domain Proteins
0
FLT1 protein, human
EC 2.7.10.1
KDR protein, human
EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-1
EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
Brachyury protein
EQ43SC3GDB
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
65-77Subventions
Organisme : Japan Society for the Promotion of Science
ID : 17H04306
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