Antitumoral effects of calcitriol in basal cell carcinomas ...mct.aacrjournals.org/content/molcanther/early/2011/08/25/1535-7163... · 1 Antitumoral effects of calcitriol in basal
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
Antitumoral effects of calcitriol in basal cell carcinomas involve inhibition of Hedgehog-
signaling and induction of vitamin D receptor-signaling and differentiation
Anja Uhmann1*, Hannah Niemann1, Bérénice Lammering1, Cornelia Henkel1, Ina Heß1,
Frauke Nitzki1, Anne Fritsch1, Nicole Prüfer1, Albert Rosenberger2, Christian Dullin3, Anke
Schraepler4, Julia Reifenberger5, Stefan Schweyer6, Torsten Pietsch7, Frank Strutz8, Walter
Schulz-Schaeffer9, Heidi Hahn1
1Institute of Human Genetics, 2Department of Genetic Epidemiology, 3Department of
Diagnostic Radiology, 4Central Animal Facility, 6Department of Pathology, 8Department of
Nephrology and Rheumatology, 9Department of Neuropathology, University of Goettingen,
Germany; 5Department of Dermatology, University of Duesseldorf, Germany; 7Department of
Neuropathology, University of Bonn, Germany
*Corresponding author:
Anja Uhmann, Institute of Human Genetics, University of Goettingen, Heinrich-Düker-Weg
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
2. Yang L, Xie G, Fan Q,Xie J. Activation of the hedgehog-signaling pathway in human cancer and the clinical implications. Oncogene 2009; 29: 469-81.
3. Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009; 361: 1164-72.
4. Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, et al. Smoothened Mutation Confers Resistance to a Hedgehog Pathway Inhibitor in Medulloblastoma. Science 2009; 326: 572-4.
5. Deeb KK, Trump DL,Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 2007; 7: 684-700.
6. Hershberger PA, Modzelewski RA, Shurin ZR, Rueger RM, Trump DL,Johnson CS. 1,25-Dihydroxycholecalciferol (1,25-D3) inhibits the growth of squamous cell carcinoma and down-modulates p21(Waf1/Cip1) in vitro and in vivo. Cancer Res 1999; 59: 2644-9.
7. Majewski S, Skopinska M, Bollag W,Jablonska S. Combination of isotretinoin and calcitriol for precancerous and cancerous skin lesions. Lancet 1994; 344: 1510-1.
8. Stewart DG,Lewis HM. Vitamin D analogues and psoriasis. J Clin Pharm Ther 1996; 21: 143-8.
9. van de Kerkhof PC. An update on vitamin D3 analogues in the treatment of psoriasis. Skin Pharmacol Appl Skin Physiol 1998; 11: 2-10.
10. Bikle DD. Vitamin D and the skin. J Bone Miner Metab 2010; 28: 117-30.
11. Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 1998; 13: 325-49.
12. Bijlsma MF, Spek CA, Zivkovic D, van de Water S, Rezaee F,Peppelenbosch MP. Repression of smoothened by patched-dependent (pro-)vitamin D3 secretion. PLoS Biol 2006; 4: e232.
13. Zibat A, Uhmann A, Nitzki F, Wijgerde M, Frommhold A, Heller T, et al. Time-point and dosage of gene inactivation determine the tumor spectrum in conditional Ptch knockouts. Carcinogenesis 2009; 30: 918-26.
14. Chen JK, Taipale J, Young KE, Maiti T,Beachy PA. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A 2002; 99: 14071-6.
15. Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, et al. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature 2000; 406: 1005-9.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
16. Nitzki F, Zibat A, König S, Wijgerde M, Rosenberger A, Brembeck FH, et al. Tumor stroma-derived Wnt5a induces differentiation of basal cell carcinoma of Ptch mutant mice via CaMKII. Cancer Res 2010; 70: 2739-48.
17. Calzada-Wack J, Kappler R, Schnitzbauer U, Richter T, Nathrath M, Rosemann M, et al. Unbalanced overexpression of the mutant allele in murine Patched mutants. Carcinogenesis 2002; 23: 727-734.
18. Banach-Petrosky W, Ouyang X, Gao H, Nader K, Ji Y, Suh N, et al. Vitamin D inhibits the formation of prostatic intraepithelial neoplasia in Nkx3.1;Pten mutant mice. Clin Cancer Res 2006; 12: 5895-901.
19. Ecke I, Rosenberger A, Obenauer S, Dullin C, Aberger F, Kimmina S, et al. Cyclopamine treatment of full-blown Hh/Ptch-associated RMS partially inhibits Hh/Ptch signaling, but not tumor growth. Mol Carcinog 2008; 47: 361-72.
20. Ma Y, Erkner A, Gong R, Yao S, Taipale J, Basler K, et al. Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched. Cell 2002; 111: 63-75.
21. Sun J, Kong J, Duan Y, Szeto FL, Liao A, Madara JL, et al. Increased NF-kappaB activity in fibroblasts lacking the vitamin D receptor. Am J Physiol Endocrinol Metab 2006; 291: E315-22.
22. Xie J, Aszterbaum M, Zhang X, Bonifas JM, Zachary C, Epstein E, et al. A role of PDGFRalpha in basal cell carcinoma proliferation. Proc Natl Acad Sci U S A 2001; 98: 9255-9.
23. Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, et al. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 1998; 391: 90-2.
24. Uhmann A, Dittmann K, Nitzki F, Dressel R, Koleva M, Frommhold A, et al. The Hedgehog receptor Patched controls lymphoid lineage commitment. Blood 2007; 110: 1814-23.
25. Mitschele T, Diesel B, Friedrich M, Meineke V, Maas RM, Gartner BC, et al. Analysis of the vitamin D system in basal cell carcinomas (BCCs). Lab Invest 2004; 84: 693-702.
26. Kamradt J, Rafi L, Mitschele T, Meineke V, Gartner BC, Wolfgang T, et al. Analysis of the vitamin D system in cutaneous malignancies. Recent Results Cancer Res 2003; 164: 259-69.
27. Reichrath J, Kamradt J, Zhu XH, Kong XF, Tilgen W,Holick MF. Analysis of 1,25-dihydroxyvitamin D(3) receptors (VDR) in basal cell carcinomas. Am J Pathol 1999; 155: 583-9.
28. Ikram MS, Neill GW, Regl G, Eichberger T, Frischauf AM, Aberger F, et al. GLI2 is expressed in normal human epidermis and BCC and induces GLI1 expression by binding to its promoter. J Invest Dermatol 2004; 122: 1503-9.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
29. Regl G, Kasper M, Schnidar H, Eichberger T, Neill GW, Ikram MS, et al. The zinc-finger transcription factor GLI2 antagonizes contact inhibition and differentiation of human epidermal cells. Oncogene 2004; 23: 1263-74.
30. Regl G, Neill GW, Eichberger T, Kasper M, Ikram MS, Koller J, et al. Human GLI2 and GLI1 are part of a positive feedback mechanism in Basal Cell Carcinoma. Oncogene 2002; 21: 5529-39.
31. Stark HJ, Breitkreutz D, Limat A, Ryle CM, Roop D, Leigh I, et al. Keratins 1 and 10 or homologues as regular constituents of inner root sheath and cuticle cells in the human hair follicle. Eur J Cell Biol 1990; 52: 359-72.
32. Beck B, Lehen'kyi V, Roudbaraki M, Flourakis M, Charveron M, Bordat P, et al. TRPC channels determine human keratinocyte differentiation: new insight into basal cell carcinoma. Cell Calcium 2008; 43: 492-505.
33. Lee SC, Ikai K, Ando Y,Imamura S. Effects of 1 alpha,25-dihydroxyvitamin D3 on the transglutaminase activity of transformed mouse epidermal cells in culture. J Dermatol 1989; 16: 7-11.
34. Bikle DD. The vitamin D receptor: a tumor suppressor in skin. Discov Med 2011; 11: 7-17.
35. Tang JY, Xiao TZ, Oda Y, Chang KS, Shpall E, Wu A, et al. Vitamin d3 inhibits hedgehog signaling and proliferation in murine Basal cell carcinomas. Cancer Prev Res (Phila) 2011; 4: 744-51.
36. Bruggemann LW, Queiroz KC, Zamani K, van Straaten A, Spek CA,Bijlsma MF. Assessing the efficacy of the hedgehog pathway inhibitor vitamin D3 in a murine xenograft model for pancreatic cancer. Cancer Biol Ther 2010; 10:
37. Varjosalo M, Li SP,Taipale J. Divergence of hedgehog signal transduction mechanism between Drosophila and mammals. Dev Cell 2006; 10: 177-86.
38. Bikle DD. Vitamin D and skin cancer. J Nutr 2004; 134: 3472S-3478S.
40. Gottlieb AB. Therapeutic options in the treatment of psoriasis and atopic dermatitis. J Am Acad Dermatol 2005; 53: S3-16.
41. Endo H, Momota Y, Oikawa A,Shinkai H. Psoriatic skin expresses the transcription factor Gli1: possible contribution of decreased neurofibromin expression. Br J Dermatol 2006; 154: 619-23.
42. Tas S,Avci O. Rapid clearance of psoriatic skin lesions induced by topical cyclopamine. A preliminary proof of concept study. Dermatology 2004; 209: 126-31.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422
Published OnlineFirst August 30, 2011.Mol Cancer Ther Anja Uhmann, Hannah Niemann, Bérénice Lammering, et al. receptor-signaling and differentiationinhibition of Hedgehog-signaling and induction of vitamin D Antitumoral effects of calcitriol in basal cell carcinomas involve
Updated version
10.1158/1535-7163.MCT-11-0422doi:
Access the most recent version of this article at:
Manuscript
Authoredited. Author manuscripts have been peer reviewed and accepted for publication but have not yet been
E-mail alerts related to this article or journal.Sign up to receive free email-alerts
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on August 30, 2011; DOI: 10.1158/1535-7163.MCT-11-0422