Inhibition of the sonic hedgehog pathway by cyplopamine reduces the CD133+/CD15+cell compartment and the in vitro tumorigenic capability of neuroblastoma cells

被引：33

作者：

Schiapparelli, Paula ^{[1
]}

Shahi, Mehdi H. ^{[1
]}

Enguita-German, Monica ^{[1
]}

Johnsen, John Inge ^{[2
]}

Kogner, Per ^{[2
]}

Lazcoz, Paula ^{[3
]}

Castresana, Javier S. ^{[1
]}

机构：

[1] Univ Navarra, Sch Sci, Brain Tumor Biol Unit CIFA, Pamplona 31008, Spain

[2] Astrid Lindgren Childrens Hosp, Karolinska Inst, Childhood Canc Res Unit, Stockholm, Sweden

[3] Univ Publ Navarra, Dept Hlth Sci, Pamplona, Spain

来源：

CANCER LETTERS | 2011年 / 310卷 / 02期

关键词：

Neuroblastoma; Sonic hedgehog; Cyclopamine; CD133; CD15; CANCER; MARKER; MEDULLOBLASTOMA; MODULATION; PROGRESS; DISEASE; TUMORS; MODEL; CD133;

D O I：

10.1016/j.canlet.2011.07.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Sonic hedgehog (Hh) developmental pathway deregulation has been proven to play an essential role in several malignancies as neuroblastoma. We found that Hh signaling is active in neuroblastoma, as most pathway components, including CLI1, were expressed in cell lines and tumor samples. Furthermore, SHH ligand expression was found in cell lines and tumors, and CM up-regulation was achieved in response to SHH treatment, suggesting an autocrine mechanism of aberrant activation. A decrease of proliferation and tumorigenic potential, as well as increased apoptosis and a dramatic decrease in the percentage of CD15+ cell population were produced upon Hh inhibition by cyclopamine. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：222 / 231

页数：10

共 23 条

[1]

Altaba ARI, 1999, DEVELOPMENT, V126, P3205

[2] HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity [J].

Clement, Virginie ;

Sanchez, Pilar ;

de Tribolet, Nicolas ;

Radovanovic, Ivan ;

Altaba, Ariel Ruiz I. .

CURRENT BIOLOGY, 2007, 17 (02) :165-172

[3] CD133+cells from medulloblastoma and PNET cell lines are more resistant to cyclopamine inhibition of the sonic hedgehog signaling pathway than CD133-cells [J].

Enguita-German, Monica ;

Schiapparelli, Paula ;

Rey, Juan A. ;

Castresana, Javier S. .

TUMOR BIOLOGY, 2010, 31 (05) :381-390

[4] Neuroblastoma cells isolated from bone marrow metastases contain a naturally enriched tumor-initiating cell [J].

Hansford, Loen M. ;

Mckee, Amy E. ;

Zhang, Libo ;

George, Rani E. ;

Gerstle, J. Ted ;

Thorner, Paul S. ;

Smith, Kristen M. ;

Look, A. Thomas ;

Yeger, Herman ;

Miller, Freda D. ;

Irwin, Meredith S. ;

Thiele, Carol J. ;

Kaplan, David R. .

CANCER RESEARCH, 2007, 67 (23) :11234-11243

[5]

Hoehner JC, 1996, LAB INVEST, V75, P659

[6] Hedgehog signaling in animal development: paradigms and principles [J].

Ingham, PW ;

McMahon, AP .

GENES & DEVELOPMENT, 2001, 15 (23) :3059-3087

[7]

Kolterud A., 2007, DRUG DISCOV TODAY TH, V4, P229

[8] Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer [J].

Kubo, M ;

Nakamura, M ;

Tasaki, A ;

Yamanaka, N ;

Nakashima, H ;

Nomura, M ;

Kuroki, S ;

Katano, M .

CANCER RESEARCH, 2004, 64 (17) :6071-6074

[9] Hedgehog signaling in pancreas development and disease [J].

Lau, J ;

Kawahira, H ;

Hebrok, M .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2006, 63 (06) :642-652

[10] Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group [J].

London, WB ;

Castleberry, RP ;

Matthay, KK ;

Look, AT ;

Seeger, RC ;

Shimada, H ;

Thorner, P ;

Brodeur, G ;

Maris, JM ;

Reynolds, CP ;

Cohn, SL .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (27) :6459-6465

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