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Science 297 (5586): 1559-1561

Copyright © 2002 by the American Association for the Advancement of Science

Medulloblastoma Growth Inhibition by Hedgehog Pathway Blockade

David M. Berman,125* Sunil S. Karhadkar,125* Andrew R. Hallahan,67 Joel I. Pritchard,7 Charles G. Eberhart,2 D. Neil Watkins,4 James K. Chen,15 Michael K. Cooper,135 Jussi Taipale,15 James M. Olson,67dagger Philip A. Beachy15dagger

Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. This compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, thus establishing a specific role for Hh pathway activity in medulloblastoma growth.

Departments of 1 Molecular Biology and Genetics, 2 Pathology, 3 Neurology, 4 Oncology, and 5 Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 6 Clinical Research Division, Fred Hutchinson Cancer Research Center, and 7 Division of Pediatric Oncology, University of Washington/Children's Hospital, Seattle WA 98105, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: jolson{at}fhcrc.org (J.M.O.) and pbeachy{at}jhmi.edu (P.A.B.)



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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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O. Ayrault, F. Zindy, J. Rehg, C. J. Sherr, and M. F. Roussel (2009)
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   Abstract »    Full Text »    PDF »
Characterization of sonic hedgehog as a novel NF-{kappa}B target gene that promotes NF-{kappa}B-mediated apoptosis resistance and tumor growth in vivo.
H. Kasperczyk, B. Baumann, K.-M. Debatin, and S. Fulda (2009)
FASEB J 23, 21-33
   Abstract »    Full Text »    PDF »
Role of Hedgehog Signaling in Ovarian Cancer.
R. Bhattacharya, J. Kwon, B. Ali, E. Wang, S. Patra, V. Shridhar, and P. Mukherjee (2008)
Clin. Cancer Res. 14, 7659-7666
   Abstract »    Full Text »    PDF »
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R. B. Corcoran, T. Bachar Raveh, M. T. Barakat, E. Y. Lee, and M. P. Scott (2008)
Cancer Res. 68, 8788-8795
   Abstract »    Full Text »    PDF »
Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas.
F. Yang, T. E. Van Meter, R. Buettner, M. Hedvat, W. Liang, C. M. Kowolik, N. Mepani, J. Mirosevich, S. Nam, M. Y. Chen, et al. (2008)
Mol. Cancer Ther. 7, 3519-3526
   Abstract »    Full Text »    PDF »
Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells.
E. Ferretti, E. De Smaele, E. Miele, P. Laneve, A. Po, M. Pelloni, A. Paganelli, L. Di Marcotullio, E. Caffarelli, I. Screpanti, et al. (2008)
EMBO J. 27, 2616-2627
   Abstract »    Full Text »    PDF »
Diagnostic and Therapeutic Stratification of Childhood Brain Tumors: Implications for Translational Research.
I. F. Pollack (2008)
J Child Neurol 23, 1179-1185
   Abstract »    PDF »
Aggressive Infantile Embryonal Tumors.
T. J. MacDonald (2008)
J Child Neurol 23, 1195-1204
   Abstract »    PDF »
Insulin receptor substrate 1 is an effector of sonic hedgehog mitogenic signaling in cerebellar neural precursors.
S. R. Parathath, L. A. Mainwaring, A. Fernandez-L, D. O. Campbell, and A. M. Kenney (2008)
Development 135, 3291-3300
   Abstract »    Full Text »    PDF »
Hedgehog: functions and mechanisms.
M. Varjosalo and J. Taipale (2008)
Genes & Dev. 22, 2454-2472
   Abstract »    Full Text »    PDF »
Dose- and Route-Dependent Teratogenicity, Toxicity, and Pharmacokinetic Profiles of the Hedgehog Signaling Antagonist Cyclopamine in the Mouse.
R. J. Lipinski, P. R. Hutson, P. W. Hannam, R. J. Nydza, I. M. Washington, R. W. Moore, G. G. Girdaukas, R. E. Peterson, and W. Bushman (2008)
Toxicol. Sci. 104, 189-197
   Abstract »    Full Text »    PDF »
Medulloblastoma Stem Cells.
X. Fan and C. G. Eberhart (2008)
J. Clin. Oncol. 26, 2821-2827
   Abstract »    Full Text »    PDF »
The Hedgehog Signaling Pathway in Cancer.
M. Evangelista, H. Tian, and F. J de Sauvage (2008)
Am. Assoc. Cancer Res. Educ. Book 2008, 479-486
   Abstract »    Full Text »    PDF »
BMPs oppose Math1 in cerebellar development and in medulloblastoma.
M. R. Grimmer and W. A. Weiss (2008)
Genes & Dev. 22, 693-699
   Full Text »    PDF »
Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development.
H. Zhao, O. Ayrault, F. Zindy, J.-H. Kim, and M. F. Roussel (2008)
Genes & Dev. 22, 722-727
   Abstract »    Full Text »    PDF »
Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma.
K. J. Briggs, I. M. Corcoran-Schwartz, W. Zhang, T. Harcke, W. L. Devereux, S. B. Baylin, C. G. Eberhart, and D. N. Watkins (2008)
Genes & Dev. 22, 770-785
   Abstract »    Full Text »    PDF »
Medulloblastoma: From Molecular Pathology to Therapy.
A. Rossi, V. Caracciolo, G. Russo, K. Reiss, and A. Giordano (2008)
Clin. Cancer Res. 14, 971-976
   Abstract »    Full Text »    PDF »
Roles for the Stem Cell Associated Intermediate Filament Nestin in Prostate Cancer Migration and Metastasis.
W. Kleeberger, G. S. Bova, M. E. Nielsen, M. Herawi, A.-Y. Chuang, J. I. Epstein, and D. M. Berman (2007)
Cancer Res. 67, 9199-9206
   Abstract »    Full Text »    PDF »
ABCG2/BCRP Expression Modulates D-Luciferin Based Bioluminescence Imaging.
Y. Zhang, J. P. Bressler, J. Neal, B. Lal, H.-E. C. Bhang, J. Laterra, and M. G. Pomper (2007)
Cancer Res. 67, 9389-9397
   Abstract »    Full Text »    PDF »
Lipoproteins and their receptors in embryonic development: more than cholesterol clearance.
T. E. Willnow, A. Hammes, and S. Eaton (2007)
Development 134, 3239-3249
   Abstract »    Full Text »    PDF »
Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists.
M. Lauth, A. Bergstrom, T. Shimokawa, and R. Toftgard (2007)
PNAS 104, 8455-8460
   Abstract »    Full Text »    PDF »
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Y. Kim, J. W. Yoon, X. Xiao, N. M. Dean, B. P. Monia, and E. G. Marcusson (2007)
Cancer Res. 67, 3583-3593
   Abstract »    Full Text »    PDF »
Identification of Cancer Stem Cell-Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line.
J. Wang, L.-P. Guo, L.-Z. Chen, Y.-X. Zeng, and S. H. Lu (2007)
Cancer Res. 67, 3716-3724
   Abstract »    Full Text »    PDF »
Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma.
C. D. Peacock, Q. Wang, G. S. Gesell, I. M. Corcoran-Schwartz, E. Jones, J. Kim, W. L. Devereux, J. T. Rhodes, C. A. Huff, P. A. Beachy, et al. (2007)
PNAS 104, 4048-4053
   Abstract »    Full Text »    PDF »
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Y.-Z. Feng, T. Shiozawa, T. Miyamoto, H. Kashima, M. Kurai, A. Suzuki, J. Ying-Song, and I. Konishi (2007)
Clin. Cancer Res. 13, 1389-1398
   Abstract »    Full Text »    PDF »
The hedgehog signaling pathway in cancer..
M. Evangelista, H. Tian, and F. J. de Sauvage (2006)
Clin. Cancer Res. 12, 5924-5928
   Abstract »    Full Text »    PDF »
Loss of cyclin D1 impairs cerebellar development and suppresses medulloblastoma formation.
J. Pogoriler, K. Millen, M. Utset, and W. Du (2006)
Development 133, 3929-3937
   Abstract »    Full Text »    PDF »
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B. A. Hatton, P. S. Knoepfler, A. M. Kenney, D. H. Rowitch, I. M. de Alboran, J. M. Olson, and R. N. Eisenman (2006)
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   Abstract »    Full Text »    PDF »
Pharmacological Activation of mGlu4 Metabotropic Glutamate Receptors Inhibits the Growth of Medulloblastomas..
L. Iacovelli, A. Arcella, G. Battaglia, S. Pazzaglia, E. Aronica, P. Spinsanti, A. Caruso, E. De Smaele, A. Saran, A. Gulino, et al. (2006)
J. Neurosci. 26, 8388-8397
   Abstract »    Full Text »    PDF »
Notch Pathway Inhibition Depletes Stem-like Cells and Blocks Engraftment in Embryonal Brain Tumors..
X. Fan, W. Matsui, L. Khaki, D. Stearns, J. Chun, Y.-M. Li, and C. G. Eberhart (2006)
Cancer Res. 66, 7445-7452
   Abstract »    Full Text »    PDF »
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J. A. Sterling, B. O. Oyajobi, B. Grubbs, S. S. Padalecki, S. A. Munoz, A. Gupta, B. Story, M. Zhao, and G. R. Mundy (2006)
Cancer Res. 66, 7548-7553
   Abstract »    Full Text »    PDF »
Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells.
R. B. Corcoran and M. P. Scott (2006)
PNAS 103, 8408-8413
   Abstract »    Full Text »    PDF »
Shh pathway activity is down-regulated in cultured medulloblastoma cells: implications for preclinical studies..
K. Sasai, J. T. Romer, Y. Lee, D. Finkelstein, C. Fuller, P. J. McKinnon, and T. Curran (2006)
Cancer Res. 66, 4215-4222
   Abstract »    Full Text »    PDF »
Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis.
J. K. Sicklick, Y.-X. Li, A. Jayaraman, R. Kannangai, Y. Qi, P. Vivekanandan, J. W. Ludlow, K. Owzar, W. Chen, M. S. Torbenson, et al. (2006)
Carcinogenesis 27, 748-757
   Abstract »    Full Text »    PDF »
alphaE-catenin controls cerebral cortical size by regulating the hedgehog signaling pathway..
W.-H. Lien, O. Klezovitch, T. E. Fernandez, J. Delrow, and V. Vasioukhin (2006)
Science 311, 1609-1612
   Abstract »    Full Text »    PDF »
Abnormal Expression of REST/NRSF and Myc in Neural Stem/Progenitor Cells Causes Cerebellar Tumors by Blocking Neuronal Differentiation.
X. Su, V. Gopalakrishnan, D. Stearns, K. Aldape, F. F. Lang, G. Fuller, E. Snyder, C. G. Eberhart, and S. Majumder (2006)
Mol. Cell. Biol. 26, 1666-1678
   Abstract »    Full Text »    PDF »
Protein Kinase C-{delta} and Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase-1 Control GLI Activation in Hedgehog Signaling.
N. A. Riobo, G. M. Haines, and C. P. Emerson Jr. (2006)
Cancer Res. 66, 839-845
   Abstract »    Full Text »    PDF »
p53-Independent Negative Regulation of p21/Cyclin-Dependent Kinase-Interacting Protein 1 by the Sonic Hedgehog-Glioma-Associated Oncogene 1 Pathway in Gastric Carcinoma Cells.
M. Ohta, K. Tateishi, F. Kanai, H. Watabe, S. Kondo, B. Guleng, Y. Tanaka, Y. Asaoka, A. Jazag, J. Imamura, et al. (2005)
Cancer Res. 65, 10822-10829
   Abstract »    Full Text »    PDF »
The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation.
T. Uziel, F. Zindy, S. Xie, Y. Lee, A. Forget, S. Magdaleno, J. E. Rehg, C. Calabrese, D. Solecki, C. G. Eberhart, et al. (2005)
Genes & Dev. 19, 2656-2667
   Abstract »    Full Text »    PDF »
Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas.
X. Ma, K. Chen, S. Huang, X. Zhang, P. A. Adegboyega, B.M. Evers, H. Zhang, and J. Xie (2005)
Carcinogenesis 26, 1698-1705
   Abstract »    Full Text »    PDF »
Targeting Medulloblastoma: Small-Molecule Inhibitors of the Sonic Hedgehog Pathway as Potential Cancer Therapeutics.
J. Romer and T. Curran (2005)
Cancer Res. 65, 4975-4978
   Abstract »    Full Text »    PDF »
Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma.
T. G. Oliver, T. A. Read, J. D. Kessler, A. Mehmeti, J. F. Wells, T. T. T. Huynh, S. M. Lin, and R. J. Wechsler-Reya (2005)
Development 132, 2425-2439
   Abstract »    Full Text »    PDF »
Sonic Hedgehog Has a Dual Effect on the Growth of Retinal Ganglion Axons Depending on Its Concentration.
A. Kolpak, J. Zhang, and Z.-Z. Bao (2005)
J. Neurosci. 25, 3432-3441
   Abstract »    Full Text »    PDF »
Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle.
M. E. Hutchin, M. S.T. Kariapper, M. Grachtchouk, A. Wang, L. Wei, D. Cummings, J. Liu, L. E. Michael, A. Glick, and A. A. Dlugosz (2005)
Genes & Dev. 19, 214-223
   Abstract »    Full Text »    PDF »
Biography of Philip A. Beachy.
M. Marino (2004)
PNAS 101, 17897-17899
   Full Text »    PDF »
Interferon-{gamma} Induced Medulloblastoma in the Developing Cerebellum.
W. Lin, A. Kemper, K. D. McCarthy, P. Pytel, J.-P. Wang, I. L. Campbell, M. F. Utset, and B. Popko (2004)
J. Neurosci. 24, 10074-10083
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The SmoA1 Mouse Model Reveals That Notch Signaling Is Critical for the Growth and Survival of Sonic Hedgehog-Induced Medulloblastomas.
A. R. Hallahan, J. I. Pritchard, S. Hansen, M. Benson, J. Stoeck, B. A. Hatton, T. L. Russell, R. G. Ellenbogen, I. D. Bernstein, P. A. Beachy, et al. (2004)
Cancer Res. 64, 7794-7800
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Inhibition of Smoothened Signaling Prevents Ultraviolet B-Induced Basal Cell Carcinomas through Regulation of Fas Expression and Apoptosis.
M. Athar, C. Li, X. Tang, S. Chi, X. Zhang, A. L. Kim, S. K. Tyring, L. Kopelovich, J. Hebert, E. H. Epstein Jr., et al. (2004)
Cancer Res. 64, 7545-7552
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The Upregulated Expression of Sonic Hedgehog in Motor Neurons after Rat Facial Nerve Axotomy.
C. Akazawa, H. Tsuzuki, Y. Nakamura, Y. Sasaki, K. Ohsaki, S. Nakamura, Y. Arakawa, and S. Kohsaka (2004)
J. Neurosci. 24, 7923-7930
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Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling.
P. Sanchez, A. M. Hernandez, B. Stecca, A. J. Kahler, A. M. DeGueme, A. Barrett, M. Beyna, M. W. Datta, S. Datta, and A. Ruiz i Altaba (2004)
PNAS 101, 12561-12566
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Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID-{beta}2m-/- repopulating cells..
M. Kobune, Y. Ito, Y. Kawano, K. Sasaki, H. Uchida, K. Nakamura, H. Dehari, H. Chiba, R. Takimoto, T. Matsunaga, et al. (2004)
Blood 104, 1002-1009
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RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma.
L. Di Marcotullio, E. Ferretti, E. De Smaele, B. Argenti, C. Mincione, F. Zazzeroni, R. Gallo, L. Masuelli, M. Napolitano, M. Maroder, et al. (2004)
PNAS 101, 10833-10838
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Molecular Profiles of Neurofibromatosis Type 1-Associated Plexiform Neurofibromas: Identification of a Gene Expression Signature of Poor Prognosis.
P. Levy, I. Bieche, K. Leroy, B. Parfait, J. Wechsler, I. Laurendeau, P. Wolkenstein, M. Vidaud, and D. Vidaud (2004)
Clin. Cancer Res. 10, 3763-3771
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Abnormalities of the vitreoretinal interface caused by dysregulated Hedgehog signaling during retinal development.
G. C.M. Black, C. J. Mazerolle, Y. Wang, K. D. Campsall, D. Petrin, B. C. Leonard, K. F. Damji, D. G. Evans, D. McLeod, and V. A. Wallace (2003)
Hum. Mol. Genet. 12, 3269-3276
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Hemangiosarcomas, Medulloblastomas, and Other Tumors in Ink4c/p53-null Mice.
F. Zindy, L. M. Nilsson, L. Nguyen, C. Meunier, R. J. Smeyne, J. E. Rehg, C. Eberhart, C. J. Sherr, and M. F. Roussel (2003)
Cancer Res. 63, 5420-5427
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Smoothened translates Hedgehog levels into distinct responses.
J. E. Hooper (2003)
Development 130, 3951-3963
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DEVELOPMENT: Longing for Ligand: Hedgehog, Patched, and Cell Death.
I. Guerrero and A. Ruiz i Altaba (2003)
Science 301, 774-776
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Sonic hedgehog.
H S Heussler and M Suri (2003)
Mol. Pathol. 56, 129-131
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Inhibition of Epithelial Ductal Branching in the Prostate by Sonic Hedgehog Is Indirectly Mediated by Stromal Cells.
B.-e. Wang, J. Shou, S. Ross, H. Koeppen, F. J. de Sauvage, and W.-Q. Gao (2003)
J. Biol. Chem. 278, 18506-18513
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Identification of a small molecule inhibitor of the hedgehog signaling pathway: Effects on basal cell carcinoma-like lesions.
J. A. Williams, O. M. Guicherit, B. I. Zaharian, Y. Xu, L. Chai, H. Wichterle, C. Kon, C. Gatchalian, J. A. Porter, L. L. Rubin, et al. (2003)
PNAS 100, 4616-4621
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How a Hedgehog might see holoprosencephaly.
E. Roessler and M. Muenke (2003)
Hum. Mol. Genet. 12, R15-25
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