Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis

K. Koga, T. Todaka, M. Morioka, J. I. Hamada, Y. Kai, S. Yano, A. Okamura, N. Takakura, T. Suda, Y. Ushio

研究成果: Article

128 引用 (Scopus)

抄録

In highly vascular malignant glioma, glioma cells themselves may express angiogenic factors and induce angiogenesis. Recent studies have shown that novel angiogenic factors, angiopoietin-1 (Ang1) and -2 (Ang2), play important roles in the modulation of vasculogenesis and angiogenesis. In this study, we determined Ang2 mRNA expression in cultured human malignant glioma cells (U105, U251, and U373 MG) by reverse transcriptase-PCR. Western blot analysis and immunocytochemical analysis with antihuman Ang2 antibody revealed that Ang2 protein was expressed and secreted by these cells. Furthermore, hypoxia increased the Ang2 protein level in cultured glioma cells. Serial sections of 32 human glioma tissues (14 glioblastomas, eight anaplastic astrocytomas, seven astrocytomas, and three pilocytic astrocytomas) were immunostained against Ang2, vascular endothelial growth factor, Tie2, von Willebrand factor, and α smooth muscle actin. The immunoreactivity of each angiogenic factor was higher in malignant gliomas than in low-grade gliomas. Ang2 protein was detected not only in endothelial cells but also in glioma cells, and its expression was prominent in both the area surrounding the necrosis and the periphery of glioblastomas. In the area surrounding necrosis, Ang2 was highly expressed and tumor vessels showed regression. In the tumor periphery, Ang2 was highly expressed and many small vessels stained positively for yon Willebrand factor but not for α smooth muscle actin, suggesting angiogenesis. Statistical analysis revealed that the Ang2 expression was negatively correlated with vessel maturation in malignant gliomas and that vascular endothelial growth factor expression was positively correlated with vessel maturation in low-grade gliomas (P < 0.05). These results suggest that glioma cells themselves express Ang2 and that expression may be induced by hypoxic stimulation and may play a crucial role in the vessel maturation, angiogenesis, and vessel regression in malignant glioma.

元の言語English
ページ(範囲)6248-6254
ページ数7
ジャーナルCancer Research
61
発行部数16
出版物ステータスPublished - 2001 8 15

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Glioma
Angiogenesis Inducing Agents
Astrocytoma
Glioblastoma
Vascular Endothelial Growth Factor A
Smooth Muscle
human ANGPT2 protein
Actins
Necrosis
Angiopoietin-2
Angiopoietin-1
Proteins
von Willebrand Factor
Reverse Transcriptase Polymerase Chain Reaction
Blood Vessels
Cultured Cells
Neoplasms
Endothelial Cells
Western Blotting
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

これを引用

Koga, K., Todaka, T., Morioka, M., Hamada, J. I., Kai, Y., Yano, S., ... Ushio, Y. (2001). Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis. Cancer Research, 61(16), 6248-6254.

Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis. / Koga, K.; Todaka, T.; Morioka, M.; Hamada, J. I.; Kai, Y.; Yano, S.; Okamura, A.; Takakura, N.; Suda, T.; Ushio, Y.

:: Cancer Research, 巻 61, 番号 16, 15.08.2001, p. 6248-6254.

研究成果: Article

Koga, K, Todaka, T, Morioka, M, Hamada, JI, Kai, Y, Yano, S, Okamura, A, Takakura, N, Suda, T & Ushio, Y 2001, 'Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis', Cancer Research, 巻. 61, 番号 16, pp. 6248-6254.
Koga K, Todaka T, Morioka M, Hamada JI, Kai Y, Yano S その他. Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis. Cancer Research. 2001 8 15;61(16):6248-6254.
Koga, K. ; Todaka, T. ; Morioka, M. ; Hamada, J. I. ; Kai, Y. ; Yano, S. ; Okamura, A. ; Takakura, N. ; Suda, T. ; Ushio, Y. / Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis. :: Cancer Research. 2001 ; 巻 61, 番号 16. pp. 6248-6254.
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abstract = "In highly vascular malignant glioma, glioma cells themselves may express angiogenic factors and induce angiogenesis. Recent studies have shown that novel angiogenic factors, angiopoietin-1 (Ang1) and -2 (Ang2), play important roles in the modulation of vasculogenesis and angiogenesis. In this study, we determined Ang2 mRNA expression in cultured human malignant glioma cells (U105, U251, and U373 MG) by reverse transcriptase-PCR. Western blot analysis and immunocytochemical analysis with antihuman Ang2 antibody revealed that Ang2 protein was expressed and secreted by these cells. Furthermore, hypoxia increased the Ang2 protein level in cultured glioma cells. Serial sections of 32 human glioma tissues (14 glioblastomas, eight anaplastic astrocytomas, seven astrocytomas, and three pilocytic astrocytomas) were immunostained against Ang2, vascular endothelial growth factor, Tie2, von Willebrand factor, and α smooth muscle actin. The immunoreactivity of each angiogenic factor was higher in malignant gliomas than in low-grade gliomas. Ang2 protein was detected not only in endothelial cells but also in glioma cells, and its expression was prominent in both the area surrounding the necrosis and the periphery of glioblastomas. In the area surrounding necrosis, Ang2 was highly expressed and tumor vessels showed regression. In the tumor periphery, Ang2 was highly expressed and many small vessels stained positively for yon Willebrand factor but not for α smooth muscle actin, suggesting angiogenesis. Statistical analysis revealed that the Ang2 expression was negatively correlated with vessel maturation in malignant gliomas and that vascular endothelial growth factor expression was positively correlated with vessel maturation in low-grade gliomas (P < 0.05). These results suggest that glioma cells themselves express Ang2 and that expression may be induced by hypoxic stimulation and may play a crucial role in the vessel maturation, angiogenesis, and vessel regression in malignant glioma.",
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AU - Kai, Y.

AU - Yano, S.

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N2 - In highly vascular malignant glioma, glioma cells themselves may express angiogenic factors and induce angiogenesis. Recent studies have shown that novel angiogenic factors, angiopoietin-1 (Ang1) and -2 (Ang2), play important roles in the modulation of vasculogenesis and angiogenesis. In this study, we determined Ang2 mRNA expression in cultured human malignant glioma cells (U105, U251, and U373 MG) by reverse transcriptase-PCR. Western blot analysis and immunocytochemical analysis with antihuman Ang2 antibody revealed that Ang2 protein was expressed and secreted by these cells. Furthermore, hypoxia increased the Ang2 protein level in cultured glioma cells. Serial sections of 32 human glioma tissues (14 glioblastomas, eight anaplastic astrocytomas, seven astrocytomas, and three pilocytic astrocytomas) were immunostained against Ang2, vascular endothelial growth factor, Tie2, von Willebrand factor, and α smooth muscle actin. The immunoreactivity of each angiogenic factor was higher in malignant gliomas than in low-grade gliomas. Ang2 protein was detected not only in endothelial cells but also in glioma cells, and its expression was prominent in both the area surrounding the necrosis and the periphery of glioblastomas. In the area surrounding necrosis, Ang2 was highly expressed and tumor vessels showed regression. In the tumor periphery, Ang2 was highly expressed and many small vessels stained positively for yon Willebrand factor but not for α smooth muscle actin, suggesting angiogenesis. Statistical analysis revealed that the Ang2 expression was negatively correlated with vessel maturation in malignant gliomas and that vascular endothelial growth factor expression was positively correlated with vessel maturation in low-grade gliomas (P < 0.05). These results suggest that glioma cells themselves express Ang2 and that expression may be induced by hypoxic stimulation and may play a crucial role in the vessel maturation, angiogenesis, and vessel regression in malignant glioma.

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