Transforming growth factor-β and stem cell markers are highly expressed around necrotic areas in glioblastoma

被引：36

作者：

Iwadate, Yasuo ^{[1
]}

Matsutani, Tomoo ^{[1
]}

Hirono, Seiichiro ^{[1
]}

Shinozaki, Natsuki ^{[1
]}

Saeki, Naokatsu ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Neurol Surg, Chuo Ku, 1-8-1 Inohana, Chiba 2602870, Japan

来源：

JOURNAL OF NEURO-ONCOLOGY | 2016年 / 129卷 / 01期

基金：

日本学术振兴会;

关键词：

Glioma; Microenvironment; Hypoxia; TGF-beta; Epithelial-mesenchymal transition; EMT; EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR MICROENVIRONMENT; GLIOMA; HYPOXIA; RESISTANCE; ANGIOGENESIS; INVASION; THERAPY; PATHWAY; GENE;

D O I：

10.1007/s11060-016-2145-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Invasion into surrounding normal brain and resistance to genotoxic therapies are the main devastating aspects of glioblastoma (GBM). These biological features may be associated with the stem cell phenotype, which can be induced through a dedifferentiation process known as epithelial-mesenchymal transition (EMT). We show here that tumor cells around pseudopalisading necrotic areas in human GBM tissues highly express the most important EMT inducer, transforming growth factor (TGF-beta), concurrently with the EMT-related transcriptional factor, TWIST. In addition, the stem cell markers CD133 and alkaline phosphatase (ALPL) were also highly expressed around necrotic foci in GBM tissues. The high expression of TGF-beta around necrotic regions was significantly correlated with shorter progression-free survival and overall survival in patients with GBM. High expression of stem cell markers, ALPL, CD133, and CD44 was also correlated with poor outcomes. These results collectively support the hypothesis that tissue hypoxia induces the stem cell phenotype through TGF-beta-related EMT and contributes to the poor outcome of GBM patients.

引用

页码：101 / 107

页数：7

共 41 条

[11] The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype [J].

Heddleston, John M. ;

Li, Zhizhong ;

McLendon, Roger E. ;

Hjelmeland, Anita B. ;

Rich, Jeremy N. .

CELL CYCLE, 2009, 8 (20) :3274-3284

[12] Molecular classification and survival prediction in human gliomas based on proteome analysis [J].

Iwadate, Y ;

Sakaida, T ;

Hiwasa, T ;

Nagai, Y ;

Ishikura, H ;

Takiguchi, M ;

Yamaura, A .

CANCER RESEARCH, 2004, 64 (07) :2496-2501

[13] Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy [J].

Jain, RK .

SCIENCE, 2005, 307 (5706) :58-62

[14] Brain tumor hypoxia: tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target [J].

Jensen, Randy L. .

JOURNAL OF NEURO-ONCOLOGY, 2009, 92 (03) :317-335

[15] Epithelial-to-mesenchymal(-like) transition as a relevant molecular event in malignant gliomas [J].

Kahlert, U. D. ;

Nikkhah, G. ;

Maciaczyk, J. .

CANCER LETTERS, 2013, 331 (02) :131-138

[16] The basics of epithelial-mesenchymal transition [J].

Kalluri, Raghu ;

Weinberg, Robert A. .

JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (06) :1420-1428

[17] Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis [J].

Kaur, B ;

Khwaja, FW ;

Severson, EA ;

Matheny, SL ;

Brat, DJ ;

Van Meir, EG .

NEURO-ONCOLOGY, 2005, 7 (02) :134-153

[18] Radiation promotes malignant progression of glioma cells through HIF-1alpha stabilization [J].

Kim, Young-Heon ;

Yoo, Ki-Chun ;

Cui, Yan-Hong ;

Uddin, Nizam ;

Lim, Eun-Jung ;

Kim, Min-Jung ;

Nam, Seon-Young ;

Kim, In-Gyu ;

Suh, Yongjoon ;

Lee, Su-Jae .

CANCER LETTERS, 2014, 354 (01) :132-141

[19] Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells [J].

Li, Zhizhong ;

Bao, Shicleng ;

Wu, Qiulian ;

Wang, Hui ;

Eyler, Christine ;

Sathornsumetee, Sith ;

Shi, Qing ;

Cao, Yiting ;

Lathia, Justin ;

McLendon, Roger E. ;

Hjelmeland, Anita B. ;

Rich, Jeremy N. .

CANCER CELL, 2009, 15 (06) :501-513

[20] Mosaic Analysis with Double Markers Reveals Tumor Cell of Origin in Glioma [J].

Liu, Chong ;

Sage, Jonathan C. ;

Miller, Michael R. ;

Verhaak, Roel G. W. ;

Hippenmeyer, Simon ;

Vogel, Hannes ;

Foreman, Oded ;

Bronson, Roderick T. ;

Nishiyama, Akiko ;

Luo, Liqun ;

Zong, Hui .

CELL, 2011, 146 (02) :209-221

← 1 2 3 4 5 →