SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

被引：141

作者：

Bareiss, Petra M. ^{[1
]}

Paczulla, Anna ^{[1
]}

Wang, Hui ^{[1
]}

Schairer, Rebekka ^{[1
]}

Wiehr, Stefan ^{[2
]}

Kohlhofer, Ursula ^{[3
]}

Rothfuss, Oliver C. ^{[4
]}

Fischer, Anna ^{[3
]}

Perner, Sven ^{[6
]}

Staebler, Annette ^{[3
]}

Wallwiener, Diethelm ^{[5
]}

Fend, Falko ^{[3
]}

Fehm, Tanja ^{[5
]}

Pichler, Bernd ^{[2
]}

Kanz, Lothar ^{[1
]}

Quintanilla-Martinez, Leticia ^{[3
]}

Schulze-Osthoff, Klaus ^{[4
,7
,8
]}

Essmann, Frank ^{[4
]}

Lengerke, Claudia ^{[1
]}

机构：

[1] Univ Tubingen, Dept Internal Med 2, Werner Siemens Fdn, Lab Preclin Imaging & Imaging Technol, D-72076 Tubingen, Germany

[2] Univ Tubingen, Dept Preclin Imaging & Radiopharm, Werner Siemens Fdn, Lab Preclin Imaging & Imaging Technol, D-72076 Tubingen, Germany

[3] Univ Tubingen, Inst Pathol, D-72076 Tubingen, Germany

[4] Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany

[5] Univ Tubingen, Womens Hosp, D-72076 Tubingen, Germany

[6] Univ Bonn, Inst Pathol, Bonn, Germany

[7] German Canc Consortium DKTK, Heidelberg, Germany

[8] German Canc Res Ctr, Heidelberg, Germany

来源：

CANCER RESEARCH | 2013年 / 73卷 / 17期

关键词：

LUNG; CD133; GENE; IDENTIFICATION; AMPLIFICATION; PLURIPOTENCY; ONCOGENE; MELANOMA; SURVIVAL; DEFINES;

D O I：

10.1158/0008-5472.CAN-12-4177

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The SRY-related HMG-box family of transcription factors member SOX2 regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, SOX2 expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies exploring the predictive value of SOX2 protein expression with respect to histopathologic and clinical parameters report contradictory results in individual tumors, indicating that SOX2 may play tumor-specific roles. In this report, we analyze the functional relevance of SOX2 expression in human ovarian carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2 expression increases the expression of CSC markers, the potential to form tumor spheres, and the in vivo tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, SOX2-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that SOX2 associates with stem cell state in ovarian carcinoma and induction of SOX2 imposes CSC properties on SOC cells. We propose the existence of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC. Cancer Res; 73(17); 5544-55. (C) 2013 AACR.

引用

页码：5544 / 5555

页数：12

共 47 条

[1]

Genetic and Epigenetic Modifications of Sox2 Contribute to the Invasive Phenotype of Malignant Gliomas [J].

Alonso, Marta M. ;

Diez-Valle, Ricardo ;

Manterola, Lorea ;

Rubio, Angel ;

Liu, Dan ;

Cortes-Santiago, Nahir ;

Urquiza, Leire ;

Jauregi, Patricia ;

Lopez de Munain, Adolfo ;

Sampron, Nicolas ;

Aramburu, Ander ;

Tejada-Solis, Sonia ;

Vicente, Carmen ;

Odero, Maria D. ;

Bandres, Eva ;

Garcia-Foncillas, Jesus ;

Idoate, Miguel A. ;

Lang, Frederick F. ;

Fueyo, Juan ;

Gomez-Manzano, Candelaria .

PLOS ONE, 2011, 6 (11)

[2]

Efficient shRNA delivery into B and T lymphoma cells using lentiviral vector-mediated transfer [J].

Anastasov N. ;

Klier M. ;

Koch I. ;

Angermeier D. ;

Höfler H. ;

Fend F. ;

Quintanilla-Martinez L. .

Journal of Hematopathology, 2009, 2 (1) :9-19

[3]

Sox2+ Adult Stem and Progenitor Cells Are Important for Tissue Regeneration and Survival of Mice [J].

Arnold, Katrin ;

Sarkar, Abby ;

Yram, Mary Anna ;

Polo, Jose M. ;

Bronson, Rod ;

Sengupta, Sumitra ;

Seandel, Marco ;

Geijsen, Niels ;

Hochedlinger, Konrad .

CELL STEM CELL, 2011, 9 (04) :317-329

[4]

Epigenetic regulation of CD133 and tumorigenicity of CD133+ovarian cancer cells [J].

Baba, T. ;

Convery, P. A. ;

Matsumura, N. ;

Whitaker, R. S. ;

Kondoh, E. ;

Perry, T. ;

Huang, Z. ;

Bentley, R. C. ;

Mori, S. ;

Fujii, S. ;

Marks, J. R. ;

Berchuck, A. ;

Murphy, S. K. .

ONCOGENE, 2009, 28 (02) :209-218

[5]

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas [J].

Bass, Adam J. ;

Watanabe, Hideo ;

Mermel, Craig H. ;

Yu, Soyoung ;

Perner, Sven ;

Verhaak, Roel G. ;

Kim, So Young ;

Wardwell, Leslie ;

Tamayo, Pablo ;

Gat-Viks, Irit ;

Ramos, Alex H. ;

Woo, Michele S. ;

Weir, Barbara A. ;

Getz, Gad ;

Beroukhim, Rameen ;

O'Kelly, Michael ;

Dutt, Amit ;

Rozenblatt-Rosen, Orit ;

Dziunycz, Piotr ;

Komisarof, Justin ;

Chirieac, Lucian R. ;

LaFargue, Christopher J. ;

Scheble, Veit ;

Wilbertz, Theresia ;

Ma, Changqing ;

Rao, Shilpa ;

Nakagawa, Hiroshi ;

Stairs, Douglas B. ;

Lin, Lin ;

Giordano, Thomas J. ;

Wagner, Patrick ;

Minna, John D. ;

Gazdar, Adi F. ;

Zhu, Chang Qi ;

Brose, Marcia S. ;

Cecconello, Ivan ;

Ribeiro, Ulysses, Jr. ;

Marie, Suely K. ;

Dahl, Olav ;

Shivdasani, Ramesh A. ;

Tsao, Ming-Sound ;

Rubin, Mark A. ;

Wong, Kwok K. ;

Regev, Aviv ;

Hahn, William C. ;

Beer, David G. ;

Rustgi, Anil K. ;

Meyerson, Matthew .

NATURE GENETICS, 2009, 41 (11) :1238-U105

[6]

The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer [J].

Chen, Yupeng ;

Shi, Lei ;

Zhang, Lirong ;

Li, Ruifang ;

Liang, Jing ;

Yu, Wenhua ;

Sun, Luyang ;

Yang, Xiaohan ;

Wang, Yan ;

Zhang, Yu ;

Shang, Yongfeng .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (26) :17969-17978

[7]

CD133 Expression Defines a Tumor Initiating Cell Population in Primary Human Ovarian Cancer [J].

Curley, Michael D. ;

Therrien, Vanessa A. ;

Cummings, Christine L. ;

Sergent, Petra A. ;

Koulouris, Carolyn R. ;

Friel, Anne M. ;

Roberts, Drucilla J. ;

Seiden, Michael V. ;

Scadden, David T. ;

Rueda, Bo R. ;

Foster, Rosemary .

STEM CELLS, 2009, 27 (12) :2875-2883

[8]

Sox genes and cancer [J].

Dong, C ;

Wilhelm, D ;

Koopman, P .

CYTOGENETIC AND GENOME RESEARCH, 2004, 105 (2-4) :442-447

[9]

In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells [J].

Dontu, G ;

Abdallah, WM ;

Foley, JM ;

Jackson, KW ;

Clarke, MF ;

Kawamura, MJ ;

Wicha, MS .

GENES & DEVELOPMENT, 2003, 17 (10) :1253-1270

[10]

The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis [J].

Fang, Xuefeng ;

Yoon, Jae-Geun ;

Li, Lisha ;

Yu, Wei ;

Shao, Jiaofang ;

Hua, Dasong ;

Zheng, Shu ;

Hood, Leroy ;

Goodlett, David R. ;

Foltz, Gregory ;

Lin, Biaoyang .

BMC GENOMICS, 2011, 12

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