Up-regulation of angiopoietin-2, matrix metalloprotease-2, membrane type 1 metalloprotease, and laminin 5 γ 2 correlates with the invasiveness of human glioma

Ping Quo, Yorihisa Imanishi, Frank C. Cackowski, Michael J. Jarzynka, Huo Quan Tao, Ryo Nishikawa, Takanori Hirose, Bo Hu*, Shi Yuan Cheng

*Corresponding author for this work

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Diffuse infiltration of malignant human glioma cells into surrounding brain structures occurs through the activation of multigenic programs. We recently showed that angiopoietin-2 (Ang2) induces glioma invasion through the activation of matrix metalloprotease-2 (MMP-2). Here, we report that up-regulation of Ang2, MMP-2, membrane type 1-MMP (MT1-MMP), and laminin 5 γ 2 (LN 5 γ 2) in tumor cells correlates with glioma invasion. Analyses of 57 clinical human glioma biopsies of World Health Organization grade I to IV tumors displaying a distinct invasive edge and 39 glioma specimens that only contain the central region of the tumor showed that Ang2, MMP-2, MT1-MMP, and LN 5 γ 2 were co-overexpressed in invasive areas but not in the central regions of the glioma tissues. Statistical analyses revealed a significant link between the preferential expression of these molecules and invasiveness. Protein analyses of microdissected primary glioma tissue showed up-regulation and activation of MT1-MMP and LN 5 γ 2 at the invasive edge of the tumors, supporting this observation. Concordantly, in human U87MG glioma xenografts engineered to express Ang2, increased expression of MT1-MMP and LN 5 γ 2, along with MMP-2 up-regulation, in actively invading glioma cells was also evident. In cell culture, stimulation of glioma cells by overexpressing Ang2 or exposure to exogenous Ang2 promoted the expression and activation of MMP-2, MT1-MMP, and LN 5 γ 2. These results suggest that up-regulation of Ang2, MMP-2, MT1-MMP, and LN 5 γ 2 is associated with the invasiveness displayed by human gliomas and that induction of these molecules by Ang2 may be essential for glioma invasion.

Original languageEnglish (US)
Pages (from-to)877-890
Number of pages14
JournalAmerican Journal of Pathology
Volume166
Issue number3
StatePublished - Jan 1 2005

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Angiopoietin-2
Metalloproteases
Glioma
Up-Regulation
Membranes
Matrix Metalloproteinases
kalinin
Neoplasms
Heterografts

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Quo, Ping ; Imanishi, Yorihisa ; Cackowski, Frank C. ; Jarzynka, Michael J. ; Tao, Huo Quan ; Nishikawa, Ryo ; Hirose, Takanori ; Hu, Bo ; Cheng, Shi Yuan. / Up-regulation of angiopoietin-2, matrix metalloprotease-2, membrane type 1 metalloprotease, and laminin 5 γ 2 correlates with the invasiveness of human glioma. In: American Journal of Pathology. 2005 ; Vol. 166, No. 3. pp. 877-890.
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abstract = "Diffuse infiltration of malignant human glioma cells into surrounding brain structures occurs through the activation of multigenic programs. We recently showed that angiopoietin-2 (Ang2) induces glioma invasion through the activation of matrix metalloprotease-2 (MMP-2). Here, we report that up-regulation of Ang2, MMP-2, membrane type 1-MMP (MT1-MMP), and laminin 5 γ 2 (LN 5 γ 2) in tumor cells correlates with glioma invasion. Analyses of 57 clinical human glioma biopsies of World Health Organization grade I to IV tumors displaying a distinct invasive edge and 39 glioma specimens that only contain the central region of the tumor showed that Ang2, MMP-2, MT1-MMP, and LN 5 γ 2 were co-overexpressed in invasive areas but not in the central regions of the glioma tissues. Statistical analyses revealed a significant link between the preferential expression of these molecules and invasiveness. Protein analyses of microdissected primary glioma tissue showed up-regulation and activation of MT1-MMP and LN 5 γ 2 at the invasive edge of the tumors, supporting this observation. Concordantly, in human U87MG glioma xenografts engineered to express Ang2, increased expression of MT1-MMP and LN 5 γ 2, along with MMP-2 up-regulation, in actively invading glioma cells was also evident. In cell culture, stimulation of glioma cells by overexpressing Ang2 or exposure to exogenous Ang2 promoted the expression and activation of MMP-2, MT1-MMP, and LN 5 γ 2. These results suggest that up-regulation of Ang2, MMP-2, MT1-MMP, and LN 5 γ 2 is associated with the invasiveness displayed by human gliomas and that induction of these molecules by Ang2 may be essential for glioma invasion.",
author = "Ping Quo and Yorihisa Imanishi and Cackowski, {Frank C.} and Jarzynka, {Michael J.} and Tao, {Huo Quan} and Ryo Nishikawa and Takanori Hirose and Bo Hu and Cheng, {Shi Yuan}",
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Up-regulation of angiopoietin-2, matrix metalloprotease-2, membrane type 1 metalloprotease, and laminin 5 γ 2 correlates with the invasiveness of human glioma. / Quo, Ping; Imanishi, Yorihisa; Cackowski, Frank C.; Jarzynka, Michael J.; Tao, Huo Quan; Nishikawa, Ryo; Hirose, Takanori; Hu, Bo; Cheng, Shi Yuan.

In: American Journal of Pathology, Vol. 166, No. 3, 01.01.2005, p. 877-890.

Research output: Contribution to journalArticle

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T1 - Up-regulation of angiopoietin-2, matrix metalloprotease-2, membrane type 1 metalloprotease, and laminin 5 γ 2 correlates with the invasiveness of human glioma

AU - Quo, Ping

AU - Imanishi, Yorihisa

AU - Cackowski, Frank C.

AU - Jarzynka, Michael J.

AU - Tao, Huo Quan

AU - Nishikawa, Ryo

AU - Hirose, Takanori

AU - Hu, Bo

AU - Cheng, Shi Yuan

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AB - Diffuse infiltration of malignant human glioma cells into surrounding brain structures occurs through the activation of multigenic programs. We recently showed that angiopoietin-2 (Ang2) induces glioma invasion through the activation of matrix metalloprotease-2 (MMP-2). Here, we report that up-regulation of Ang2, MMP-2, membrane type 1-MMP (MT1-MMP), and laminin 5 γ 2 (LN 5 γ 2) in tumor cells correlates with glioma invasion. Analyses of 57 clinical human glioma biopsies of World Health Organization grade I to IV tumors displaying a distinct invasive edge and 39 glioma specimens that only contain the central region of the tumor showed that Ang2, MMP-2, MT1-MMP, and LN 5 γ 2 were co-overexpressed in invasive areas but not in the central regions of the glioma tissues. Statistical analyses revealed a significant link between the preferential expression of these molecules and invasiveness. Protein analyses of microdissected primary glioma tissue showed up-regulation and activation of MT1-MMP and LN 5 γ 2 at the invasive edge of the tumors, supporting this observation. Concordantly, in human U87MG glioma xenografts engineered to express Ang2, increased expression of MT1-MMP and LN 5 γ 2, along with MMP-2 up-regulation, in actively invading glioma cells was also evident. In cell culture, stimulation of glioma cells by overexpressing Ang2 or exposure to exogenous Ang2 promoted the expression and activation of MMP-2, MT1-MMP, and LN 5 γ 2. These results suggest that up-regulation of Ang2, MMP-2, MT1-MMP, and LN 5 γ 2 is associated with the invasiveness displayed by human gliomas and that induction of these molecules by Ang2 may be essential for glioma invasion.

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