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Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas

Oncogene volume 21, pages 6598–6605 (2002)Cite this article

Abstract

The diverse receptor-ligand pairs of the Wnt and frizzled (Fz) families play important roles during embryonic development, and thus may be overexpressed in cancers that arise from immature cells. Hence, we investigated the expression and function of five Wnt (Wnt-1, 5a, 7a, 10b, 13) and two Fz (Fz-2, 5) genes in 10 head and neck squamous carcinoma cell lines (HNSCC). In comparison to normal bronchial or oral epithelial cells, all the HNSCC had markedly increased mRNA levels of Wnt-1, 7a, 10b, and 13, as well as Fz-2. Moreover, the levels of Wnt-1, 10b, and Fz-2 proteins were also markedly increased in HNSCC, relative to normal epithelial cells. Treatment of one HNSCC cell line (SNU 1076) with anti-Wnt-1 antibodies reduced the activity of the Wnt/Fz dependent transcription factor LEF/TCF, and diminished the expression of cyclin D1 and β-catenin proteins. Blocking Wnt-1 signaling also inhibited proliferation and induced apoptosis in these cells. These results show that HNSCC cell lines often overexpress one or more Wnt and Fz genes, and suggest that the growth and survival of a subset of HNSCC may depend on the Wnt/Fz pathway. Hence, the Wnt and Fz receptors may be possible targets for immunotherapy therapy of this common cancer.

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References

  • Aoki M, Hecht A, Kruse U, Kemler R, Vogt PK . 1999 Proc. Natl. Acad. Sci. USA 96: 139–144

  • Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W . 1996 Nature 382: 638–642

  • Cadigan KM, Nusse R . 1997 Genes Dev. 11: 3286–3305

  • Hunter T . 1997 Cell 88: 333–346

  • Kim SY, Chu KC, Lee HR, Lee KS, Carey TE . 1997 Acta Otolaryngol. 117: 775–784

  • Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H . 1997 Science 275: 1784–1787

  • Ku JL, Kim WH, Lee JH, Park HS, Kim KH, Sung MW, Park JG . 1999 Laryngoscope 109: 976–982

  • Landis SH, Murray T, Bolden S, Wingo PA . 1999 CA Cancer J. Clin. 49: 8–31

  • Leethanakul C, Patel V, Gillespie J, Pallente M, Ensley JF, Koontongkaew S, Liotta LA, Emmert-Buck M, Gutkind JS . 2000 Oncogene 19: 3220–3224

  • Miller JR, Hocking AM, Brown JD, Moon RT . 1999 Oncogene 18: 7860–7872

  • Ng JK, Tamura K, Buscher D, Izpisua-Belmonte JC . 1999 Curr. Top. Dev. Biol. 41: 37–66

  • Nusse R, Varmus HE . 1982 Cell 31: 99–109

  • Parkin DM, Pisani P, Ferlay J . 1999 CA Cancer J. Clin. 49: 33–64

  • Parr BA, Shea MJ, Vassileva G, McMahon AP . 1993 Development 119: 247–261

  • Ramsdell AF, Yost HJ . 1998 Trends Genet. 14: 459–465

  • Riddle RD, Ensini M, Nelson C, Tsuchida T, Jessell TM, Tabin C . 1995 Cell 83: 631–640

  • Sagara N, Toda G, Hirai M, Terada M, Katoh M . 1998 Biochem. Biophys. Res. Comm. 252: 117–122

  • Uren A, Reichsman F, Anest V, Taylor WG, Muraiso K, Battaro DP, Cumberledge S, Rubin JS . 2000 J. Biol. Chem. 275: 4374–4382

  • Vogel A, Rodriguez C, Warnken W, Izpisua Belmonte JC . 1995 Nature 378: 716–720

  • Whiteside TL, Sung MW, Nagashima S, Chikamatsu K, Okada K, Vujanovic NL . 1998 Clin. Cancer Res. 4: 1135–1145

  • Yasumura S, Hirabayashi H, Schwartz DR, Toso JF, Johnson JT, Herberman RB, Whiteside TL . 1993 Cancer Res. 53: 1461–1468

  • Yoganathan TN, Costello P, Chen X, Jabali M, Yan J, Lenng D, Zhang Z, Yee A, Dedhar S, Senghera J . 2000 Biochem. Pharmacol. 60: 1115–1119

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Acknowledgements

We would like to thank Michael Rosenbach, Rommel Tawatao and Jessica Wei for technical assistance. We are grateful to Nancy Noon for secretarial support, and to The University of California San Diego, Center for AIDS Research Genomics Core Laboratory for performing the real-time PCR. This work was funded in part by NIH grant GM23200, and the UC Biotechnology Strategic Targets for Alliances in Research Project (BioSTAR). C.-S. Rhee was supported by the Postdoctoral Abroad Training Program (01-14-10-2) of the Korea Science and Engineering Foundation, and the Training Abroad Fund of Seoul National University Hospital.

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Authors and Affiliations

  1. Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, California, 92093-0663, CA, USA

    Chae-Seo Rhee, Malini Sen, Desheng Lu, Christina Wu, Lorenzo Leoni, Maripat Corr & Dennis A Carson

  2. Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea

    Chae-Seo Rhee

  3. National Cancer Institute, Bethesda, Maryland, USA

    Jeffrey Rubin

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  1. Chae-Seo Rhee
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Correspondence to Dennis A Carson.

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Rhee, CS., Sen, M., Lu, D. et al. Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas. Oncogene 21, 6598–6605 (2002). https://doi.org/10.1038/sj.onc.1205920

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