Arsenic trioxide inhibits tumor cell growth in malignant rhabdoid tumors in vitro and in vivo by targeting overexpressed Gli1

被引：43

作者：

Kerl, Kornelius ^{[1
,2
]}

Moreno, Natalia ^{[1
]}

Holsten, Till ^{[1
]}

Ahlfeld, Julia ^{[3
]}

Mertins, Julius ^{[1
]}

Hotfilder, Marc ^{[2
]}

Kool, Marcel ^{[4
]}

Bartelheim, Kerstin ^{[5
]}

Schleicher, Sabine ^{[6
]}

Handgretinger, Rupert ^{[6
]}

Schueller, Ulrich ^{[3
]}

Meisterernst, Michael ^{[1
]}

Fruehwald, Michael C. ^{[2
,5
]}

机构：

[1] Univ Munster, Inst Mol Tumor Biol, D-48149 Munster, Germany

[2] Univ Childrens Hosp Muenster, Dept Pediat Hematol & Oncol, Munster, Germany

[3] Univ Munich, Ctr Neuropathol, Munich, Germany

[4] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[5] Childrens Hosp Augsburg, Swabian Childrens Canc Ctr, Augsburg, Germany

[6] Univ Tubingen, Univ Childrens Hosp, Dept Pediat Hematol & Oncol, Tubingen, Germany

来源：

INTERNATIONAL JOURNAL OF CANCER | 2014年 / 135卷 / 04期

关键词：

arsenic trioxide; rhabdoid tumors; Sonic hedgehog; Gli1; ATYPICAL TERATOID/RHABDOID TUMORS; ACUTE PROMYELOCYTIC LEUKEMIA; HEDGEHOG PATHWAY INHIBITOR; MEDULLOBLASTOMA; ACTIVATION; ANTAGONISTS; EXPRESSION; RESISTANCE; CANCER; MICE;

D O I：

10.1002/ijc.28719

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Rhabdoid tumors are highly aggressive tumors occurring in infants and very young children. Despite multimodal and intensive therapy prognosis remains poor. Molecular analyses have uncovered several deregulated pathways, among them the CDK4/6-Rb-, the WNT- and the Sonic hedgehog (SHH) pathways. The SHH pathway is activated in rhabdoid tumors by GLI1 overexpression. Here, we demonstrate that arsenic trioxide (ATO) inhibits tumor cell growth of malignant rhabdoid tumors in vitro and in a mouse xenograft model by suppressing Gli1. Our data uncover ATO as a promising therapeutic approach to improve prognosis for rhabdoid tumor patients.

引用

页码：989 / 995

页数：7

共 26 条

[1] Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors
Alarcon-Vargas, D
Zhang, Z
Agarwal, B
Challagulla, K
Mani, S
Kalpana, GV
[J]. ONCOGENE, 2006, 25 (05) : 722 - 734
[2] Determinants of cerebrospinal fluid arsenic concentration in patients with acute promyelocytic leukemia on oral arsenic trioxide therapy
Au, Wing-Yan
Tam, Sidney
Fong, Bonnie M.
Kwong, Yok-Lam
[J]. BLOOD, 2008, 112 (09) : 3587 - 3590
[3] Tissue repair and stem cell renewal in carcinogenesis
Beachy, PA
Karhadkar, SS
Berman, DM
[J]. NATURE, 2004, 432 (7015) : 324 - 331
[4] Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway
Beauchamp, Elspeth M.
Ringer, Lymor
Bulut, Gulay
Sajwan, Kamal P.
Hall, Michael D.
Lee, Yi-Chien
Peaceman, Daniel
Oezdemirli, Metin
Rodriguez, Olga
Macdonald, Tobey J.
Albanese, Chris
Toretsky, Jeffrey A.
Uren, Aykut
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (01) : 148 - 160
[5] High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival
Birks, Diane K.
Donson, Andrew M.
Patel, Purvi R.
Dunham, Christopher
Muscat, Andrea
Algar, Elizabeth M.
Ashley, David M.
Kleinschmidt-DeMasters, B. K.
Vibhakar, Rajeev
Handler, Michael H.
Foreman, Nicholas K.
[J]. NEURO-ONCOLOGY, 2011, 13 (12) : 1296 - 1307
[6] A phase I trial of arsenic trioxide chemoradiotherapy for infiltrating astrocytomas of childhood
Cohen, Kenneth J.
Gibbs, Iris C.
Fisher, Paul G.
Hayashi, Robert J.
Macy, Margaret E.
Gore, Lia
[J]. NEURO-ONCOLOGY, 2013, 15 (06) : 783 - 787
[7] High-resolution genomic analysis suggests the absence of recurrent genomic alterations other than SMARCB1 aberrations in atypical teratoid/rhabdoid tumors
Hasselblatt, Martin
Isken, Sarah
Linge, Anna
Eikmeier, Kristin
Jeibmann, Astrid
Oyen, Florian
Nagel, Inga
Richter, Julia
Bartelheim, Kerstin
Kordes, Uwe
Schneppenheim, Reinhard
Fruehwald, Michael
Siebert, Reiner
Paulus, Werner
[J]. GENES CHROMOSOMES & CANCER, 2013, 52 (02) : 185 - 190
[8] Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway
Jagani, Zainab
Mora-Blanco, E. Lorena
Sansam, Courtney G.
McKenna, Elizabeth S.
Wilson, Boris
Chen, Dongshu
Klekota, Justin
Tamayo, Pablo
Nguyen, Phuong T. L.
Tolstorukov, Michael
Park, Peter J.
Cho, Yoon-Jae
Hsiao, Kathy
Buonamici, Silvia
Pomeroy, Scott L.
Mesirov, Jill P.
Ruffner, Heinz
Bouwmeester, Tewis
Luchansky, Sarah J.
Murtie, Joshua
Kelleher, Joseph F.
Warmuth, Markus
Sellers, William R.
Roberts, Charles W. M.
Dorsch, Marion
[J]. NATURE MEDICINE, 2010, 16 (12) : 1429 - U112
[9] Itraconazole and Arsenic Trioxide Inhibit Hedgehog Pathway Activation and Tumor Growth Associated with Acquired Resistance to Smoothened Antagonists
Kim, James
Aftab, Blake T.
Tang, Jean Y.
Kim, Daniel
Lee, Alex H.
Rezaee, Melika
Kim, Jynho
Chen, Baozhi
King, Emily M.
Borodovsky, Alexandra
Riggins, Gregory J.
Epstein, Ervin H., Jr.
Beachy, Philip A.
Rudin, Charles M.
[J]. CANCER CELL, 2013, 23 (01) : 23 - 34
[10] Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus
Kim, Jynho
Kato, Masaki
Beachy, Philip A.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (51) : 21666 - 21671

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