Skip to main content

Advertisement

Log in

Establishment and characterization of a novel human malignant peripheral nerve sheath tumor cell line, FMS-1, that overexpresses epidermal growth factor receptor and cyclooxygenase-2

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. We established a new human MPNST cell line (designated FMS-1) from MPNST of the right brachial plexus of a 69-year-old woman with NF1. The cell line has been maintained for >24 months with >100 passages. FMS-1 cells showed a fibrosarcoma-like or epithelioid pattern in the heterotransplanted tumor, compared with a fascicular growth pattern of short-spindle tumor cells in the primary tumor. Immunophenotypically, FMS-1 cells showed almost the same characteristics as the primary tumor. Cytogenetic and molecular analyses revealed a deletion in exons 5-8 of the p53 gene. Epidermal growth factor receptor (EGFR) and cyclooxygenase (COX)-2 were expressed in FMS-1 cells. To improve the highly aggressive course and poor prognosis and establish new therapeutic methods, molecular genetic and biological characterizations of MPNST are required. Thus, FMS-1 cells might be useful for investigating biological behaviors and developing new molecular-targeting antitumor drugs for MPNST expressing EGFR or COX-2.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Woodruff JM, Kourea HP, Louis DN et al (2000) Malignant peripheral nerve sheath tumour (MPNST). In: Kleihues P, Cavenee WK (eds) World Health Organization classification of tumours. Tumours of the nervous system. IARC Press, Lyon, pp 172–174

    Google Scholar 

  2. Weiss SW, Goldblum JR (2007) Malignant tumors of the peripheral nerves. In: Weiss SW, Goldblum JR (eds) Enzinger and Weiss's soft tissue tumors, 5th edn. Mosby/Elsevier, Philadelphia, pp 903–917

    Google Scholar 

  3. Grobmyer SR, Reith JD, Shahlaee A et al (2008) Malignant peripheral nerve sheath tumor: molecular pathogenesis and current management considerations. J Surg Oncol 97:340–349

    Article  PubMed  CAS  Google Scholar 

  4. Ono I, Ishiwata I, Nakaguchi T et al (1989) Establishment and characterization of a human malignant schwannoma cell line (HKMS). Hum Cell 2:272–277 (in Japanese with English abstract)

    PubMed  CAS  Google Scholar 

  5. Nagashima Y, Ohaki Y, Tanaka Y et al (1990) Establishment of an epithelioid malignant schwannoma cell line (YST-1). Virchows Arch [B] 59:321–327

    Article  CAS  Google Scholar 

  6. Reynolds JE, Fletcher JA, Lytle CH et al (1992) Molecular characterization of a 17q11.2 translocation in a malignant schwannoma cell line. Hum Genet 90:450–456

    Article  PubMed  CAS  Google Scholar 

  7. Imaizumi S, Motoyama T, Ogose A et al (1998) Characterization and chemosensitivity of two human malignant peripheral nerve sheath tumour cell lines derived from a patient with neurofibromatosis type 1. Virchows Arch 433:435–441

    Article  PubMed  CAS  Google Scholar 

  8. Sonobe H, Takeuchi T, Furihata M et al (2000) A new human malignant peripheral nerve sheath tumour-cell line, HS-sch-2, harbouring p53 point mutation. Int J Oncol 17:347–352

    PubMed  CAS  Google Scholar 

  9. Aoki M, Nabeshima K, Nishio J et al (2006) Establishment of three malignant peripheral nerve sheath tumor cell lines, FU-SFT8611, 8710 and 9817: conventional and molecular cytogenetic characterization. Int J Oncol 29:1421–1428

    PubMed  Google Scholar 

  10. Fletcher CDM, Dal Cin P, de Wever I et al (1999) Correlation between clinicopathological features and karyotype in spindle cell sarcomas. A report of 130 cases from the CHAMP study group. Am J Pathol 154:1841–1847

    PubMed  CAS  Google Scholar 

  11. Fletcher CDM (2000) Peripheral neuroectodermal tumors. In: Fletcher CDM (ed) Diagnostic histopathology of tumors, 2nd edn. Churchill Livingstone, London, pp 1695–1698

    Google Scholar 

  12. Murakami Y, Hayashi K, Sekiya T (1991) Detection of aberrations the p53 alleles and the gene transcript in human tumor cell lines by single-strand conformation polymorphism analysis. Cancer Res 51:3356–3361

    PubMed  CAS  Google Scholar 

  13. Hakozaki M, Hojo H, Sato M et al (2006) Establishment and characterization of a new cell line, FRTK-1, derived from human malignant rhabdoid tumor of the kidney, with overexpression of epidermal growth factor receptor and cyclooxygenase-2. Oncol Rep 16:265–271

    PubMed  CAS  Google Scholar 

  14. Hakozaki M, Hojo H, Sato M et al (2006) Establishment and characterization of a new cell line, FPS-1, derived from human undifferentiated pleomorphic sarcoma, overexpressing epidermal growth factor receptor and cyclooxygenase-2. Anticancer Res 26:3393–3401

    PubMed  CAS  Google Scholar 

  15. Carroll SL, Stonecypher MS (2004) Tumor suppressor mutations and growth factor signaling in the pathogenesis of NF1-associated peripheral nerve sheath tumors. I. The role of tumor suppressor mutations. J Neuropathol Exp Neurol 63:1115–1123

    PubMed  CAS  Google Scholar 

  16. Bottillo I, Ahlquist T, Brekke H et al (2009) Germline and somatic NF1 mutations in sporadic and NF1-associated malignant peripheral nerve sheath tumours. J Pathol 217:693–701

    Article  PubMed  CAS  Google Scholar 

  17. Legius E, Marchuk DA, Collins FS et al (1993) Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. Nat Genet 3:122–126

    Article  PubMed  CAS  Google Scholar 

  18. Menon AG, Anderson KM, Riccardi VM et al (1990) Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. Proc Natl Acad Sci USA 87:5435–5439

    Article  PubMed  CAS  Google Scholar 

  19. Legius E, Dierick H, Wu R et al (1994) TP53 mutations are frequent in malignant NF1 tumors. Genes Chromosomes Cancer 10:250–255

    Article  PubMed  CAS  Google Scholar 

  20. Lothe RA, Slettan A, Saeter G et al (1995) Alterations at chromosome 17 loci in peripheral nerve sheath tumors. J Neuropathol Exp Neurol 54:65–73

    Article  PubMed  CAS  Google Scholar 

  21. Bridge RS Jr, Bridge JA, Neff JR et al (2004) Recurrent chromosomal imbalances and structurally abnormal breakpoints within complex karyotypes of malignant peripheral nerve sheath tumour and malignant triton tumour: a cytogenetic and molecular cytogenetic study. J Clin Pathol 57:1172–1178

    Article  PubMed  CAS  Google Scholar 

  22. Birindelli S, Perrone F, Oggionni M et al (2001) Rb and TP53 pathway alterations in sporadic and NF1-related malignant peripheral nerve sheath tumors. Lab Invest 81:833–844

    PubMed  CAS  Google Scholar 

  23. Mawrin C, Kirches E, Boltze C et al (2002) Immunohistochemical and molecular analysis of p53, RB, and PTEN in malignant peripheral nerve sheath tumors. Virchows Arch 440:610–615

    Article  PubMed  CAS  Google Scholar 

  24. Davidoff AM, Pence JC, Shorter NA et al (1992) Expression of p53 in human neuroblastoma- and neuroepithelioma-derived cell lines. Oncogene 7:127–133

    PubMed  CAS  Google Scholar 

  25. Villuendas R, Piris MA, Algara P et al (1993) The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations. Blood 82:3151–3156

    PubMed  CAS  Google Scholar 

  26. Lepelley P, Preudhomme C, Vanrumbeke M et al (1994) Detection of p53 mutations in hematological malignancies: comparison between immunocytochemistry and DNA analysis. Leukemia 8:1342–1349

    PubMed  CAS  Google Scholar 

  27. Nicholson RI, Gee JM, Harper ME (2001) EGFR and cancer prognosis. Eur J Cancer 37:S9–S15

    Article  PubMed  CAS  Google Scholar 

  28. Holbro T, Civenni G, Hynes N (2003) The ErbB receptors and their role in cancer progression. Exp Cell Res 284:99–110

    Article  PubMed  CAS  Google Scholar 

  29. Dobashi Y, Takei N, Suzuki S et al (2004) Aberration of epidermal growth factor receptor expression in bone and soft-tissue tumors: protein overexpression, gene amplification and activation of downstream molecules. Mod Pathol 17:1497–1505

    Article  PubMed  CAS  Google Scholar 

  30. Yamamoto T, Fujita I, Akisue T et al (2004) Amphiregulin and epidermal growth factor receptor expression in human malignant fibrous histiocytoma of soft tissues. Anticancer Res 24:1307–1310

    PubMed  CAS  Google Scholar 

  31. Beech D, Pollock RE, Tsan R et al (1998) Epidermal growth factor receptor and insulin-like growth factor-I receptor expression and function in human soft-tissue sarcoma cells. Int J Oncol 12:329–336

    PubMed  CAS  Google Scholar 

  32. Abdiu A, Walz TM, Nishikawa BK et al (1998) Human malignant fibrous histiocytomas in vitro: growth characteristics and their association with expression of mRNA for platelet-derived growth factor, transforming growth factor-alpha and their receptors. Eur J Cancer 34:2094–2100

    Article  PubMed  CAS  Google Scholar 

  33. Tawbi H, Thomas D, Lucas DR et al (2008) Epidermal growth factor receptor expression and mutational analysis in synovial sarcomas and malignant peripheral nerve sheath tumors. Oncologist 13:459–466

    Article  PubMed  CAS  Google Scholar 

  34. Holtkamp N, Malzer E, Zietsch J et al (2008) EGFR and erbB2 in malignant peripheral nerve sheath tumors and implications for targeted therapy. Neuro Oncol 10:946–957

    Article  PubMed  CAS  Google Scholar 

  35. Vane JR, Bakhle YS, Botting RM (1998) Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38:97–120

    Article  PubMed  CAS  Google Scholar 

  36. Dubois RN, Abramson SB, Crofford L et al (1998) Cyclooxygenase in biology and disease. FASEB J 12:1063–1073

    PubMed  CAS  Google Scholar 

  37. Gately S, Li WW (2004) Multiple roles of COX-2 in tumor angiogenesis: a target for antiangiogenic therapy. Semin Oncol 31:2–11

    Article  PubMed  CAS  Google Scholar 

  38. Yamashita H, Osaki M, Honjo S et al (2003) A selective cyclooxygenase-2 inhibitor, NS-398, inhibits cell growth by cell cycle arrest in a human malignant fibrous histiocytoma cell line. Anticancer Res 23:4671–4676

    PubMed  CAS  Google Scholar 

  39. Naruse T, Nishida Y, Hosono K et al (2006) Meloxicam inhibits osteosarcoma growth, invasiveness and metastasis by COX-2-dependent and independent routes. Carcinogenesis 27:584–592

    Article  PubMed  CAS  Google Scholar 

  40. Hakozaki M, Hojo H, Kikuchi S et al (2007) Etodolac, a selective cyclooxygenase-2 inhibitor, induces apoptosis by activating caspases in human malignant rhabdoid tumor cells (FRTK-1). Oncol Rep 17:169–173

    PubMed  CAS  Google Scholar 

  41. Naruse T, Nishida Y, Ishiguro N (2007) Synergistic effects of meloxicam and conventional cytotoxic drugs in human MG-63 osteosarcoma cells. Biomed Pharmacother 61:338–346

    Article  PubMed  CAS  Google Scholar 

  42. Lee EJ, Choi EM, Kim SR et al (2007) Cyclooxygenase-2 promotes cell proliferation, migration and invasion in U2OS human osteosarcoma cells. Exp Mol Med 39:469–476

    PubMed  CAS  Google Scholar 

  43. Liu B, Shi ZL, Feng J et al (2008) Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt. Cell Biol Int 32:494–501

    Article  PubMed  CAS  Google Scholar 

  44. Dannenberg AJ, Lippman SM, Mann JR et al (2005) Cyclooxygenase-2 and epidermal growth factor receptor: pharmacologic targets for chemoprevention. J Clin Oncol 23:254–266

    Article  PubMed  CAS  Google Scholar 

  45. Lippman SM, Gibson N, Subbaramaiah K et al (2005) Combined targeting of the epidermal growth factor receptor and cyclooxygenase-2 pathways. Clin Cancer Res 11:6097–6099

    Article  PubMed  CAS  Google Scholar 

  46. Tortora G, Caputo R, Damiano V et al (2003) Combination of a selective cyclooxygenase-2 inhibitor with epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 and protein kinase A antisense causes cooperative antitumor and antiangiogenic effect. Clin Cancer Res 9:1566–1572

    PubMed  CAS  Google Scholar 

  47. Chen Z, Zhang X, Li M et al (2004) Simultaneously targeting epidermal growth factor receptor tyrosine kinase and cyclooxygenase-2, an efficient approach to inhibition of squamous cell carcinoma of the head and neck. Clin Cancer Res 10:5930–5939

    Article  PubMed  CAS  Google Scholar 

  48. Zhang X, Chen ZG, Choe MS et al (2005) Tumor growth inhibition by simultaneously blocking epidermal growth factor receptor and cyclooxygenase-2 in a xenograft model. Clin Cancer Res 11:6261–6269

    Article  PubMed  CAS  Google Scholar 

  49. Melisi D, Caputo R, Damiano V et al (2005) Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer. Endocr Relat Cancer 12:1051–1058

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Mrs. Hiromi Kaneko and Miss Satomi Hikichi for their skillful technical assistance.

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michiyuki Hakozaki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hakozaki, M., Hojo, H., Sato, M. et al. Establishment and characterization of a novel human malignant peripheral nerve sheath tumor cell line, FMS-1, that overexpresses epidermal growth factor receptor and cyclooxygenase-2. Virchows Arch 455, 517–526 (2009). https://doi.org/10.1007/s00428-009-0848-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-009-0848-1

Keywords

Navigation