Hedgehog targeting by cyclopamine suppresses head and neck squamous cell carcinoma and enhances chemotherapeutic effects

Anticancer Research

Volumn 33, Issue 6, 2013, Pages 2415-2424

  Mozet, Christian ^a   Stoehr, Matthaeus ^a   Dimitrova, Kamelia ^a   Dietz, Andreas ^a   Wichmann, Gunnar ^a  

^a UNIVERSITY OF LEIPZIG   (Germany)

Author keywords

Cisplatin; Cyclopamine; Docetaxel; Head and neck squamous cell carcinoma (HNSCC); Hedgehog pathway; Synergism

Indexed keywords

CISPLATIN; CYCLOPAMINE; CYTOKERATIN; DOCETAXEL; FLUORESCENT DYE; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; ANTINEOPLASTIC AGENT; G PROTEIN COUPLED RECEPTOR; KERATIN; SMO PROTEIN, HUMAN; TAXOID; VERATRUM ALKALOID;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER PATIENT; CARCINOMA CELL; CELL PROLIFERATION; CLINICAL ARTICLE; COLONY FORMATION; CONTROLLED STUDY; CYTOTOXICITY; DILUTION; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG TARGETING; EX VIVO STUDY; FEMALE; GROWTH INHIBITION; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; IC 50; IMMUNOHISTOCHEMISTRY; MALE; MAXIMUM PLASMA CONCENTRATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; TUMOR BIOPSY; TUMOR CELL CULTURE; BIOSYNTHESIS; CELL STRAIN KB; DRUG EFFECT; DRUG SCREENING; HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC); HEAD AND NECK TUMOR; HEDGEHOG PATHWAY; METABOLISM; MOLECULARLY TARGETED THERAPY; SQUAMOUS CELL CARCINOMA; SYNERGISM;

CISPLATIN; CYCLOPAMINE; DOCETAXEL; HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC); HEDGEHOG PATHWAY; SYNERGISM;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, SQUAMOUS CELL; CISPLATIN; FEMALE; HEAD AND NECK NEOPLASMS; HEDGEHOG PROTEINS; HUMANS; KB CELLS; KERATINS; MALE; MOLECULAR TARGETED THERAPY; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION; TAXOIDS; TUMOR CELLS, CULTURED; TUMOR STEM CELL ASSAY; VERATRUM ALKALOIDS;

MLCS; MLOWN;

EID: 84881352043     PISSN: 02507005     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (51)

1. Zigon G, Berrino F, Gatta G, Sanchez MJ, van Dijk B, Van Eycken E, Francisci S and the EUROCARE Working Group: Prognoses for head and neck cancers in Europe diagnosed in 1995-1999: A population-based study. Ann Oncol 22: 165-174, 2011.
2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics 58: 71-96, 2008.
3. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK and Ang KK: Radiotherapy plus cetuximab for squamous cell carcinoma of the head and neck. N Engl J Med 354: 567-578, 2006.
4. Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, Knecht R, Amellal N, Schueler A and Baselga J: Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 25: 2171-2177, 2007.
5. Thomas GR, Nadiminti H and Regalado J: Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int J Exp Pathol 86: 347-363, 2005.
6. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernandez-del Castillo C, Yajnik V, Antoniu B, McMahon M, Warshaw AL and Hebrok M: Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425: 851-856, 2003.
7. Azoulay S, Terry S, Chimingqi M, Sirab N, Faucon H, Gil Diez de Medina S, Moutereau S, Maille P, Soyeux P, Abbou C, Salomon L, Vacherot F, de La Taille A, Loric S and Allory Y: Comparative expression of hedgehog ligands at different stages of prostate carcinoma progression. J Pathol 216: 460-470, 2008.
8. Mukherjee S, Frolova N, Sadlonova A, Novak Z, Steg A, Page GP, Welch DR, Lobo-Ruppert SM, Ruppert JM, Johnson MR and Frost AR: Hedgehog signaling and response to cyclopamine differ in epithelial and stromal cells in benign breast and breast cancer. Cancer Biol Ther 5: 674-683, 2006.
9. Ma X, Chen K, Huang S, Zhang X, Adegboyega PA, Evers BM, Zhang H and Xie J: Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. Carcinogenesis 26: 1698-1705, 2005.
10. Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC and Hauschild A: Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 366: 2171-2179, 2012
11. Chung CH, Dignam J, Hammond ME, Magliocco AM, Jordan R, Trotti A, Spencer S, Cooper JS, Le Q and Ang K: Association of high GLI1 expression with poor survival in head and neck cancer patients treated with radiation therapy (RTOG 9003). J Clin Oncol ASCO Ann Meet Proc (Post-Meeting Edition) 28: 34s, 2010.
12. Schneider S, Thurnher D, Kloimstein P, Leitner V, Petzelbauer P, Pammer J, Brunner M and Erovic BM: Expression of the sonic hedgehog pathway in squamous cell carcinoma of the skin and the mucosa of the head and neck. Head Neck 33: 244-250, 2011.
13. Wang YF, Chang CJ, Lin CP, Chang SY, Chu PY, Tai SK, Li WY, Chao KS and Chen YJ: Expression of hedgehog signaling molecules as a prognostic indicator of oral squamous cell carcinoma. Head Neck 34: 1556-1561, 2012.
14. Dimitrova K, Stoehr M, Dehghani F, Dietz A, Wichmann G, Bertolini J and Mozet C: Overexpression of the Hedgehog Signalling Pathway in Head and Neck Squamous Cell Carcinoma. Onkologie in press, 2013.
15. Dietz A, Boehm A, Mozet C, Wichmann G, and Giannis A: Current aspects of targeted therapy in head and neck tumors. Eur Arch Otorhinolaryngol 265: 3-12, 2008.
16. Dietz A, Boehm A, Horn IS, Kruber P, Bechmann I, Golusinski W, Niederwieser D, Dollner R, Remmerbach TW, Wittekind C, Dietzsch S, Hildebrandt G and Wichmann G: Assay-based response evaluation in head and neck oncology: Requirements for better decision making. Eur Arch Otorhinolaryngol 267: 483-494, 2010.
17. Wichmann G, Horn IS, Boehm A, Mozet C, Tschop K, Dollner R and Dietz A: Single tissue samples from head and neck squamous cell carcinomas are representative regarding the entire tumor's chemosensitivity to cisplatin and docetaxel. Onkologie 32: 264-272, 2009.
18. Horn IS, Wichmann G, Mozet C, Dietz A, Dollner R, Tschop K and Boehm A: Heterogeneity of epithelial and stromal cells of head and neck squamous cell carcinomas in ex vivo chemoresponse. Cancer Chemother Pharmacol 65: 1153-1163, 2010.
19. American Joint Committee on Cancer: Comparison Guide. Cancer Staging Manual Fifth versus Sixth Edition 2009 http://www.cancer-staging.org/products/ ajccgiude.pdf.
20. Dollner R, Kopun M, Dietz A, Wiessler M and Granzow C: Chemoreactivity profiling of HNSCC: Equipotentiality of platinum compounds and glufosfamide, a novel alkylating agent. Proc Am Assn Cancer Res 43: 926-931, 2004.
21. Dollner R, Granzow C, Helmke BM, Ruess A, Schad A and Dietz A: The impact of stromal cell contamination on chemosensitivity testing of head and neck carcinoma. Anticancer Res 24: 325-331, 2004.
22. Desoize B, Berthiot G, Manot L, Coninx P and Dumont P: Evaluation of a prediction model of cisplatin dose based on total platinum plasma concentration. Eur J Cancer 32: 1734-1738, 1996.
23. Bissett D, Setanoians A, Cassidy J, Graham MA, Chadwick GA, Wilson P, Auzannet V, Le Bail N, Kaye SB and Kerr DJ: Phase I and pharmacokinetic study of taxotere (RP 56976) administered as a 24-hour infusion. Cancer Res 53: 523-527, 1993.
24. Jin ZJ: About the evaluation of drug combinations. Acta Pharmacol Sin 25: 146-147, 2004.
25. Weitzman JB: Agonizing hedgehog. J Biol 1: 7, 2002.
26. Li X, Deng W, Nail CD, Bailey SK, Kraus MH, Ruppert JM and Lobo-Ruppert SM: SNAIL induction is an early response to GLI1 that determines the efficiency of epithelial transformation. Oncogene 25: 609-621, 2006.
27. Lee SW, Moskowitz MA and Sims JR: Sonic hedgehog inversely regulates the expression of angiopoietin-1 and angiopoietin-2 in fibroblasts. Int J Mol Med 19: 445-451, 2007.
28. Athar M, Li C, Tang X, Chi S, Zhang X, Kim AL, Tyring SK, Kopelovich L, Hebert J, Epstein EH Jr., Bickers DR and Xie J: Inhibition of smoothened signaling prevents ultraviolet Binduced basal cell carcinomas through regulation of FAS expression and apoptosis. Cancer Res 64: 7545-7552, 2004.
29. Adolphe C, Hetherington R, Ellis T, Wainwright B. Patched1 functions as a gatekeeper by promoting cell cycle progression. Cancer Res 66: 2081-2088, 2006.
30. Beachy PA, Karhadkar SS and Berman DM: Tissue repair and stem cell renewal in carcinogenesis. Nature 432: 324-331, 2004.
31. Sims-Mourtada J, Izzo JG, Apisarnthanarax S, Wu TT, Malhotra U, Luthra R, Liao Z, Komaki R, van der Kogel A, Ajani J and Chao KS: Hedgehog: An attribute to tumor regrowth after chemoradiotherapy and a target to improve radiation response. Clin Cancer Res 12: 6565-6572, 2006.
32. Chen YJ, Sims-Mourtada J, Izzo J and Chao KS: Targeting the hedgehog pathway to mitigate treatment resistance. Cell Cycle 6: 1826-1830, 2007.
33. Yoshikawa R, Nakano Y, Tao L, Koishi K, Matsumoto T, Sasako M, Tsujimura T, Hashimoto-Tamaoki T and Fujiwara Y: Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy. Br J Cancer 98: 1670-1674, 2008.
34. Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, Gervaz P and Ruiz i Altaba A: Human colon cancer epithelial cells harbour active Hedgehog-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med 1: 338-351, 2009.
35. Keysar SB and Jimeno A: More than markers: Biological significance of cancer stem cell-defining molecules. Mol Cancer Ther 9: 2450-2457, 2010.
36. Incardona JP, Gaffield W, Kapur RP and Roelink H: The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development 125: 3553-3562, 1998.
37. Cooper MK, Porter JA, Young KE and Beachy PA: Teratogenmediated inhibition of target tissue response to SHH signaling. Science 280: 1603-1607, 1998.
38. Chen JK, Taipale J, Cooper MK and Beachy PA: Inhibition of Hedgehog signaling by direct binding of cyclopamine to smoothened. Genes Dev 16: 2743-2748, 2002.
39. Feldmann G, Dhara S, Fendrich V, Bedja D, Beaty R, Mullendore M, Karikari C, Alvarez H, Lacobuzio-Donahue C, Jimeno A, Gabrielson KL, Matsui W and Maitra A: Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res 67: 2187-2196, 2007.
40. Feldmann G, Fendrich V, McGovern K, Bedja D, Bisht S, Alvarez H, Koorstra JB, Habbe N, Karikari C, Mullendore M, Gabrielson KL, Sharma R, Matsui W and Maitra A: An orally bioavailable small-molecule inhibitor of hedgehog signaling inhibits tumour initiation and metastasis in pancreatic cancer. Mol Cancer Ther 7: 2725-2735, 2008.
41. Romer J and Curran T: Targeting medulloblastoma: Smallmolecule inhibitors of the sonic hedgehog pathway as potential cancer therapeutics. Cancer Res 65: 4975-4978, 2005.
42. Datta S and Datta MW: Sonic hedgehog signaling in advanced prostate cancer. Cell Mol Life Sci 63: 435-448, 2006.
43. Dahmane N, Sanchez P, Gitton Y, Palma V, Sun T, Beyna M, Weiner H and Ruiz i Altaba A: The sonic hedgehog-GLI pathway regulates dorsal brain growth and tumorigenesis. Development 128: 5201-5212, 2001.
44. Bar EE, Chaudhry A, Lin A, Fan X, Schreck K, Matsui W, Piccirillo S, Vescovi AL, DiMeco F, Olivi A and Eberhart CG: Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells 25: 2524-2533, 2007.
45. Sanchez P and Ruiz i Altaba A: In vivo inhibition of endogenous brain tumours through systemic interference of hedgehog signaling in mice. Mech Dev 122: 223-230, 2005.
46. Park KS, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR, Bernard K, Conklin JF, Szczepny A, Yuan J, Guo R, Ospina B, Falzon J, Bennett S, Brown TJ, Markovic A, Devereux WL, Ocasio CA, Chen JK, Stearns T, Thomas RK, Dorsch M, Buonamici S, Watkins DN, Peacock CD and Sage J: A crucial requirement for hedgehog signaling in small cell lung cancer. Nat Med 17: 1504-1508, 2011.
47. Bahra M, Kamphues C, Boas-Knoop S, Lippert S, Esendik U, Schuller U, Hartmann W, Waha A, Neuhaus P, Heppner F, Pietsch T and Koch A: Combination of hedgehog signaling blockade and chemotherapy leads to tumor reduction in pancreatic adenocarcinomas. Pancreas 41: 222-229, 2012.
48. Schrader C, Boehm A, Reiche A, Dietz A, Mozet C and Wichmann G: Combined effects of lapatinib and cisplatin on colony formation of head and neck squamous cell carcinoma. Anticancer Res 32: 3191-3199, 2012.
49. Lipinski RJ, Hutson PR, Hannam PW, Nydza RJ, Washington IM, Moore RW, Girdaukas GG, Peterson RE and Bushman W: Dose-And route-dependent teratogenicity, toxicity, and pharmacokinetic profiles of the hedgehog signaling antagonist cyclopamine in the mouse. Toxicol Sci 104: 189-197, 2008.
50. Keeler RF: Teratogenic effects of cyclopamine and jervine in rats, mice and hamsters. Proc Soc Exp Biol Med 149: 302-306, 1975.
51. Peukert S and Miller-Moslin K: Small-molecule inhibitors of the hedgehog signaling pathway as cancer therapeutics. Chem Med Chem 5: 500-512, 2010.