Skip to main content
SpringerLink
Log in

Upregulation of IGF2 is associated with an acquired resistance for cis-diamminedichloroplatinum in human head and neck squamous cell carcinoma

  • Head and Neck
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Ten head and neck squamous cell carcinoma (HNSCC) cell lines that had acquired cis-diamminedichloroplatinum (CDDP) resistance were successfully established by means of in vitro culture with CDDP. Flow cytometry analysis showed the significantly decreased induction of apoptosis after the CDDP treatment in the acquired CDDP-resistant sublines. Among these, RPMI2650CR showed a 9.38-fold increased IC50 in comparison with the parental cell line, RPMI2650. The identification of the resistance-related gene clusters was conducted between RPMI2650CR and RPMI2650 using two distinct microarray platforms. The expressional profiles were quite similar, suggesting that a limited number of genes regulate the acquisition of CDDP resistance. IGF2 was found to be one of the candidates for acquired CDDP-resistance. The introduction of IGF2 into RPMI2650 caused CDDP resistance along with suppression of CDDP-dependent apoptosis. On the other hand, siRNA-mediated knockdown of IGF2 caused reduction of acquired CDDP-resistance in RPMI2650CR. These results demonstrate that expression of IGF2 plays an important and critical role in CDDP resistance in a HNSCC cell line RPMI2650. These findings suggest the possibility for developing a new strategy for treating patients with HNSCC, particularly those with acquired CDDP resistance, by combining CDDP with inhibition of the IGF2 pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ferlay J, Bray F, Pisani P, Parkin DM (2004) GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC Cancer Base, No5, ver. 20. IARC Press, Lyon

    Google Scholar 

  2. Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J (2003) Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349:2091–2098

    Article  CAS  PubMed  Google Scholar 

  3. Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA (2003) An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 21:92–98

    Article  PubMed  Google Scholar 

  4. Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M (2004) European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350:1945–1952

    Article  CAS  PubMed  Google Scholar 

  5. Ogawa T, Furukawa T, Shiga K, Hashimoto S, Ogawa K, Kobayashi T, Horii A (2010) A cDNA microarray analysis identifies 52 genes associated with CDDP susceptibility in head and neck squamous cell carcinoma cell lines. Eur Arch Otorhinolaryngol 267:123–129

    Article  Google Scholar 

  6. Higuchi EE, Oridate N, Furuta Y, Suzuki S, Hatakeyama H, Sawa H, Sunayashiki-Kusuzaki K, Yamazaki K, Inuyama Y, Fukuda S (2003) Differentially expressed genes associated with CIS-diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and cDNA microarray. Head Neck 25:187–193

    Article  PubMed  Google Scholar 

  7. Hockley SL, Mathijs K, Staal YC, Brewer D, Giddings I, van Delft JH, Phillips DH (2009) Interlaboratory and interplatform comparison of microarray gene expression analysis of HepG2 cells exposed to benzo(a)pyrene. OMICS 13:115–125

    Article  CAS  PubMed  Google Scholar 

  8. Iwasaki I, Sugiyama H, Kanazawa S, Hemmi H (2002) Establishment of cisplatin-resistant variant of human nouroblastoma cell lines, TWG and GOTO, and their drug cross resistance profiles. Cancer Chemother Pharmacol 49:438–444

    Article  CAS  PubMed  Google Scholar 

  9. Tounekti O, Belehradek J Jr, Mir LM (1995) Relationships between DNA fragmentation, chromatin condensation, and changes in flow cytometry profiles detected during apoptosis. Exp Cell Res 217:506–516

    Article  CAS  PubMed  Google Scholar 

  10. Yamanaka S, Sunamura M, Furukawa T, Sun L, Lefter LP, Abe T, Yatsuoka T, Fujimura H, Shibuya E, Kotobuki N, Oshimura M, Sakurada A, Sato M, Kondo T, Matsuno S, Horii A (2004) Chromosome 12, frequently deleted in human pancreatic cancer, may encode a tumor suppressor gene that suppresses angiogenesis. Lab Invest 84:1339–1351

    Article  CAS  PubMed  Google Scholar 

  11. Furukawa T, Kanai N, Shiwaku HO, Soga N, Uehara A, Horii A (2006) AURKA is one of the downstream targets of MAPK1/ERK2 in pancreatic cancer. Oncogene 25:4831–4839

    Article  CAS  PubMed  Google Scholar 

  12. Mori Y, Shiwaku H, Fukushige S, Wakatsuki S, Sato M, Nukiwa T, Horii A (1997) Alternative splicing of hMSH2 in normal human tissues. Hum Genet 99:590–595

    Article  CAS  PubMed  Google Scholar 

  13. Xu S, Furukawa T, Kanai N, Sunamura M, Horii A (2005) Abrogation of DUSP6 by hypermethylation in human pancreatic cancer. J Hum Genet 50:159–167

    Article  CAS  PubMed  Google Scholar 

  14. Ogawa K, Shiga K, Saijo S, Ogawa T, Kimura N, Horii A (2006) A novel G106D alteration of the SDHD gene in a pedigree with familial paraganglioma. Am J Med Genet A 140:2441–2446

    PubMed  Google Scholar 

  15. Kondo E, Horii A, Fukushige S (1999) The human PMS2L proteins do not interact with hMLH1, a major DNA mismatch repair protein. J Biochem 125:818–825

    CAS  PubMed  Google Scholar 

  16. Yatsuoka T, Furukawa T, Sunamura M, Matsuno S, Horii A (2004) TU12B1-TY, a novel gene in the region at 12q22–q23.1 frequently deleted in pancreatic cancer, shows reduced expression in pancreatic cancer cells. Oncol Rep 12:1263–1268

    CAS  PubMed  Google Scholar 

  17. Andrews PA, Howell SB (1990) Cellular pharmacology of cisplatin: perspectives on mechanisms of acquired resistance. Cancer Cells 2:35–43

    CAS  PubMed  Google Scholar 

  18. Hoskins LK, Whelan RD, Shellard SA, Bedford P, Hill BT (1990) An evaluation of the role of glutathione and its associated enzymes in the expression of differential sensitivities to antitumor agents shown by a range of human tumour cell lines. Biochem Pharmacol 40:1833–1842

    Article  Google Scholar 

  19. Hospers GA, Meijer C, de Leij L, Uges DR, Mulder NH, de Vries EG (1990) A study of human small-cell lung carcinoma (hSCLC) cell lines with different sensitivities to detect relevant mechanisms of cisplatin (CDDP) resistance. Int J Cancer 46:138–144

    Article  CAS  PubMed  Google Scholar 

  20. Meijer C, Mulder NH, Timmer-Bosscha H, Sluiter WJ, Meersma GJ, de Vries EG (1992) Relationship of cellular glutathione to the cytotoxicity and resistance of seven platinum compounds. Cancer Res 52:6885–6889

    CAS  PubMed  Google Scholar 

  21. Robbins KT, Vicario D, Seagren S, Weisman R, Pellitteri P, Kerber C, Orloff L, Los G, Howell SB (1994) A targeted superdose cisplatin chemoradiation protocol for advanced head and neck cancer. Am J Surg 168:419–422

    Article  CAS  PubMed  Google Scholar 

  22. Eckstein N, Servan K, Hildebrandt B, Pölitz A, von Jonquières G, Wolf-Kümmeth S, Napierski I, Hamacher A, Kassack MU, Budczies J, Beier M, Dietel M, Royer-Pokora B, Denkert C, Royer HD (2009) Hyperactivation of the insulin-like growth factor receptor I signaling pathway is an essential event for cisplatin resistance of ovarian cancer cells. Cancer Res 69:2996–3003

    Article  CAS  PubMed  Google Scholar 

  23. Ogawa O, Eccles MR, Szeto J, McNoe LA, Yun K, Maw MA, Smith PJ, Reeve AE (1993) Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms’ tumour. Nature 362:749–751

    Article  CAS  PubMed  Google Scholar 

  24. Sait SN, Nowak NJ, Singh-Kahlon P, Weksberg R, Squire J, Shows TB, Higgins MJ (1994) Localization of Beckwith-Wiedemann and rhabdoid tumor chromosome rearrangements to a defined interval in chromosome band 11p15.5. Genes Chromosomes Cancer 11:97–105

    Article  CAS  PubMed  Google Scholar 

  25. Winkler R, Delacroix L, Bensbaho K, Lambert S, Collette J, Hodzic D (1999) IGF-II in primary human colorectal tumors: Peptide level, activated promoters, parental imprinting and gene rearrangement. Horm Metab Res 31:148–154

    Article  CAS  PubMed  Google Scholar 

  26. Xu W, Fan H, He X, Zhang J, Xie W (2006) LOI of IGF2 is associated with esophageal cancer and linked to methylation status of IGF2 DMR. J Exp Clin Cancer Res 25:543–547

    CAS  PubMed  Google Scholar 

  27. LeRoith D, Roberts CT Jr (2003) The insulin-like growth factor system and cancer. Cancer Lett 195:127–137

    CAS  PubMed  Google Scholar 

  28. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM (1997) Meltzer PS, AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277:965–968

    Article  CAS  PubMed  Google Scholar 

  29. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM (1997) Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell 90:569–580

    Article  CAS  PubMed  Google Scholar 

  30. Cartee L, Kucera GL (2000) Protein kinase C modulation and anticancer drug response. Cancer Invest 18:731–739

    Article  CAS  PubMed  Google Scholar 

  31. Beck J, Bohnet B, Brügger D, Bader P, Dietl J, Scheper RJ, Kandolf R, Liu C, Niethammer D, Gekeler V (1998) Multiple gene expression analysis reveals distinct differences between G2 and G3 stage breast cancers, and correlations of PKC eta with MDR1, MRP and LRP gene expression. Br J Cancer 77:87–91

    CAS  PubMed  Google Scholar 

  32. Beck JF, Bohnet B, Brügger D, Dietl J, Scheper RJ, Bader P, Niethammer D, Gekeler V (1998) Expression analysis of protein kinase C isozymes and multidrug resistance associated genes in ovarian cancer cells. Anticancer Res 18:701–705

    CAS  PubMed  Google Scholar 

  33. Sonnemann J, Gekeler V, Ahlbrecht K, Brischwein K, Liu C, Bader P, Müller C, Niethammer D, Beck JF (2004) Down-regulation of protein kinase Ceta by antisense oligonucleotides sensitises A549 lung cancer cells to vincristine and paclitaxel. Cancer Lett 209:177–185

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Mami Mori (Tohoku University School of Medicine) for her excellent secretarial assistance in the preparation of this manuscript, and to Biomedical Research Core of Tohoku University Graduate School of Medicine for technical support. This work was supported in part by Grants-in-Aid and Academic Frontier Project for Private Universities: matching fund subsidy 2006–2010 from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

Conflict of interest statement

We have no conflict of interest, potential conflicts or financial relationships.

Author information

Authors and Affiliations

  1. Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Miyagi, 980-8575, Japan

    Takenori Ogawa, Kazumi Ogawa, Toru Furukawa & Akira Horii

  2. Department of Otolaryngology and Head and Neck Surgery, Tohoku University School of Medicine, Sendai, Miyagi, 980-8574, Japan

    Takenori Ogawa, Kazumi Ogawa, Kiyoto Shiga, Sho Hashimoto & Toshimitsu Kobayashi

  3. Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine, Itabashi-ku, Tokyo, 173-8610, Japan

    Hiroki Nagase

Authors
  1. Takenori Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazumi Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kiyoto Shiga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toru Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroki Nagase
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sho Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshimitsu Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Akira Horii
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Takenori Ogawa or Akira Horii.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ogawa, T., Ogawa, K., Shiga, K. et al. Upregulation of IGF2 is associated with an acquired resistance for cis-diamminedichloroplatinum in human head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 267, 1599–1606 (2010). https://doi.org/10.1007/s00405-010-1257-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-010-1257-4

Keywords

Search

Navigation