Shh pathway activity is down-regulated in cultured medulloblastoma cells: implications for preclinical studies

Cancer Research
Ken SasaiTom Curran

Abstract

Gene expression profiling indicates that the Sonic Hedgehog (Shh) pathway is active in approximately 30% of human medulloblastomas, suggesting that it could provide a useful therapeutic target. Previously, we showed that spontaneous medulloblastomas in Ptc1(+/-)p53-/- mice could be eradicated by treatment with a small-molecule inhibitor (HhAntag) of Smoothened (Smo). Here, we compared the responses of mouse medulloblastoma cells propagated in flank allografts, either directly or after culture in vitro, to HhAntag. We found that Shh pathway activity was suppressed in medulloblastoma cells cultured in vitro and it was not restored when these cells were transplanted into the flank of nude mice. The growth of these transplanted tumor cells was not inhibited by treatment of mice with doses of HhAntag that completely suppressed Smo activity. Interestingly, tumor cells transplanted directly into the flank maintained Smo activity and were sensitive to treatment with HhAntag. These findings indicate that propagation of tumor cells in culture inhibits Smo activity in a way that cannot be reversed by transplantation in vivo, and they raise concerns about the use of cultured tumor cells to test the efficacy of Shh pathway inhibitors as ant...Continue Reading

References

Aug 15, 1977·International Journal of Cancer. Journal International Du Cancer·R M McAllisterM B Gardner
Nov 1, 1985·Journal of Neuropathology and Experimental Neurology·H S FriedmanD D Bigner
Apr 16, 1998·Journal of the National Cancer Institute·W C ZamboniP J Houghton
Nov 24, 1999·Genes, Chromosomes & Cancer·R H ZurawelC Raffel
Apr 18, 2001·Current Opinion in Oncology·M ChintagumpalaS M Blaney
Jun 18, 2002·Nature Genetics·Michael D TaylorDavid Hogg
Aug 31, 2002·Science·David M BermanPhilip A Beachy
Apr 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Juliet A WilliamsFrank Y Wang
Oct 2, 2003·Nature·Sarah P ThayerMatthias Hebrok
Nov 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Joshua B RubinRosalind A Segal
Mar 31, 2004·The Lancet Oncology·Richard J Gilbertson
May 4, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·L R Kelland
Sep 14, 2004·Nature·Sunil S KarhadkarPhilip A Beachy
Sep 24, 2004·Cancer Cell·Eric C Holland
Jan 15, 2005·Trends in Molecular Medicine·Silvia Marino
Apr 5, 2005·Oncogene·Hiromichi KimuraTom Curran

❮ Previous
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Citations

Jun 20, 2008·Breast Cancer Research and Treatment·Xiaomei ZhangMichael T Lewis
Mar 25, 2009·Journal of Medicinal Chemistry·Neeraj MahindrooNaoaki Fujii
May 27, 2011·Nature Reviews. Cancer·Jessica M Y Ng, Tom Curran
Dec 2, 2006·Nature Reviews. Drug Discovery·Lee L Rubin, Frederic J de Sauvage
Oct 2, 2009·Nature Reviews. Drug Discovery·Bin-Bing S ZhouPeter B Dirks
Mar 2, 2011·Nature Reviews. Drug Discovery·Giordano Caponigro, William R Sellers
Apr 25, 2007·Oncogene·Y LeeP J McKinnon
Jan 28, 2009·Genes & Development·Jessica D KesslerRobert J Wechsler-Reya
Feb 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alessandra RossiAntonio Giordano
Aug 4, 2012·Molecular Cancer Research : MCR·Rosa F HwangRobert Godin
May 20, 2009·The Journal of Clinical Investigation·Martin L SosRoman K Thomas
Mar 18, 2011·Toxicologic Pathology·Jillian L BrechbielTom Curran
Nov 26, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Yoon-Jae ChoScott L Pomeroy
Oct 28, 2009·PloS One·Jay JooWilliam A May
Jun 21, 2011·International Journal of Molecular Sciences·Ruixin ZhuZhiwei Cao
Apr 7, 2010·Asian Journal of Andrology·Lluis A Lopez-Barcons
Aug 20, 2010·EMBO Molecular Medicine·Tom Curran
May 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Matthias LauthRune Toftgård
Jun 22, 2014·Neuro-oncology·Mark W Kieran
Jun 10, 2009·Expert Opinion on Therapeutic Patents·Martin R TremblayAlfredo C Castro
Jul 18, 2015·Genes·Emanuela Felley-BoscoMayura Meerang
Feb 18, 2010·Expert Opinion on Drug Discovery·Georg FeldmannAnirban Maitra
May 1, 2009·Expert Opinion on Drug Discovery·Paola GallinariChristian Steinkühler
Aug 22, 2012·Pharmacology & Therapeutics·Fergal C KelleherDavid M Thomas
Mar 6, 2012·Seminars in Radiation Oncology·Thomas B BrunnerMichael Baumann
May 16, 2009·Trends in Pharmacological Sciences·Suzie J Scales, Frederic J de Sauvage
Mar 12, 2015·Cancer Cell·Hayley J SharpeFrederic J de Sauvage
Nov 11, 2011·International Journal of Cancer. Journal International Du Cancer·Pietro FerruzziAnnette Bakker
Aug 29, 2006·Biochemical and Biophysical Research Communications·Hideki UchikawaToshiyuki Miyashita
Mar 19, 2013·Biochemical Pharmacology·Jan de WeilleNorbert Bakalara
Nov 27, 2007·Developmental Biology·Vincent LelievreJames A Waschek
Sep 17, 2016·Expert Review of Anticancer Therapy·Nicholas J CollierJohn T Lear
Oct 19, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jun YangWenfu Tan

❮ Previous
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