Prognostic significance of VEGF receptors expression on the tumor cells in skull base chordoma

Yukina Morimoto, Ryota Tamura, Kentaro Ohara, Kenzo Kosugi, Yumiko Oishi, Yuki Kuranari, Kazunari Yoshida, Masahiro Toda

Research output: Contribution to journalArticle

Abstract

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: 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: 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: Expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to tumor growth in patients with chordomas.

Original languageEnglish
JournalJournal of Neuro-Oncology
DOIs
Publication statusPublished - 2019 Jan 1

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Chordoma
Vascular Endothelial Growth Factor Receptor
Skull Base
Neoplasms
Vascular Endothelial Growth Factor A
Tumor Microenvironment
Macrophages
Vascular Endothelial Growth Factor Receptor-1
Notochord
Regulatory T-Lymphocytes
Immunosuppressive Agents
Growth
Tumor Cell Line
Blood Vessels
Endothelial Cells

Keywords

  • Chordoma
  • Endothelial cell
  • Programmed death-ligand 1
  • Regulatory T-cells
  • Tumor-associated macrophage
  • Vascular endothelial growth factor receptor

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Prognostic significance of VEGF receptors expression on the tumor cells in skull base chordoma. / Morimoto, Yukina; Tamura, Ryota; Ohara, Kentaro; Kosugi, Kenzo; Oishi, Yumiko; Kuranari, Yuki; Yoshida, Kazunari; Toda, Masahiro.

In: Journal of Neuro-Oncology, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "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: 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: 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: Expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to tumor growth in patients with chordomas.",
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AU - Morimoto, Yukina

AU - Tamura, Ryota

AU - Ohara, Kentaro

AU - Kosugi, Kenzo

AU - Oishi, Yumiko

AU - Kuranari, Yuki

AU - Yoshida, Kazunari

AU - Toda, Masahiro

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AB - 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: 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: 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: Expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to tumor growth in patients with chordomas.

KW - Chordoma

KW - Endothelial cell

KW - Programmed death-ligand 1

KW - Regulatory T-cells

KW - Tumor-associated macrophage

KW - Vascular endothelial growth factor receptor

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