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Virchows Archiv
Published in: Virchows Archiv 3/2007

01-09-2007 | Original Article

Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation

Authors: Naoko Kudo, Akira Ogose, Tetsuo Hotta, Hiroyuki Kawashima, Wenguang Gu, Hajime Umezu, Tsuyoshi Toyama, Naoto Endo

Published in: Virchows Archiv | Issue 3/2007

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Abstract

Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade sarcoma coexists with a low-grade chondroid tumor. We herein review a case of dedifferentiated chondrosarcoma with an osteosarcoma omit component that occurred in the distal femur of a 38-year-old man. We established the cell line (NDCS-1) from a pleural effusion of the metastatic lung tumor. The cell line was characterized by a the G-banded karyotype, polymerase chain reaction (PCR) single-strand conformation polymorphism analysis, spectral karyotyping, and reverse transcriptase PCR (RT-PCR). The tumor exhibited complex karyotypes and a high frequency of chromosomal amplication with p53 mutation. This tumor revealed an osteoblastic and chondroblastic character in vitro and in severe combined immunodeficiency mice. The expression and phosphorylation of platelet-derived growth factor receptor-β, which seemed to play a major role in the malignant phenotype of chondrosarcoma, was confirmed by RT-PCR and Western blotting. To our knowledge, this is the first report of the establishment of a human dedifferentiated chondrosarcoma.
Literature
1.
Aigner T (2002) Towards a new understanding and classification of chondrogenic neoplasias of the skeleton–biochemistry and cell biology of chondrosarcoma and its variants. Virchows Arch 441:219–230PubMedCrossRef
2.
Aigner T, Unni KK (1999) Is dedifferentiated chondrosarcoma a “de-differentiated” chondrosarcoma? J Pathol 189:445–447PubMedCrossRef
3.
Basciani S, Mariani S, Arizzi M, Brama M, Ricci A, Betsholtz C, Bondjers C, Ricci G, Catizone A, Galdieri M, Spera G, Gnessi L (2004) Expression of platelet-derived growth factor (PDGF) in the epididymis and analysis of the epididymal development in PDGF-A, PDGF-B, and PDGF receptor beta deficient mice. Biol Reprod 70:168–177PubMedCrossRef
4.
Bayani J, Zielenska M, Pandita A, Al-Romaih K, Karaskova J, Harrison K, Bridge JA, Sorensen P, Thorner P, Squire JA (2003) Spectral karyotyping identifies recurrent complex rearrangements of chromosomes 8, 17, and 20 in osteosarcomas. Genes Chromosomes Cancer 36:7–16PubMedCrossRef
5.
Beppu K, Jaboine J, Merchant MS, Mackall CL, Thiele CJ (2004) Effect of imatinib mesylate on neuroblastoma tumorigenesis and vascular endothelial growth factor expression. J Natl Cancer Inst 96:46–55PubMedCrossRef
6.
Bovee JV, Cleton-Jansen AM, Kuipers-Dijkshoorn NJ, van den Broek LJ, Taminiau AH, Cornelisse CJ, Hogendoorn PC (1999) Loss of heterozygosity and DNA ploidy point to a diverging genetic mechanism in the origin of peripheral and central chondrosarcoma. Genes Chromosomes Cancer 26:237–246PubMedCrossRef
7.
Bovee JV, Cleton-Jansen AM, Rosenberg C, Taminiau AH, Cornelisse CJ, Hogendoorn PC (1999) Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis. J Pathol 189:454–462PubMedCrossRef
8.
Bovee JV, Sciot R, Cin PD, Debiec-Rychter M, Zelderen-Bhola SL, Cornelisse CJ, Hogendoorn PC (2001) Chromosome 9 alterations and trisomy 22 in central chondrosarcoma: a cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes. Diagn Mol Pathol 10:228–235PubMedCrossRef
9.
Bridge JA, DeBoer J, Travis J, Johansson SL, Elmberger G, Noel SM, Neff JR (1994) Simultaneous interphase cytogenetic analysis and fluorescence immunophenotyping of dedifferentiated chondrosarcoma. Implications for histopathogenesis. Am J Pathol 144:215–220PubMed
10.
Bruns J, Fiedler W, Werner M, Delling G (2005) Dedifferentiated chondrosarcoma—a fatal disease. J Cancer Res Clin Oncol 131:333–339PubMedCrossRef
11.
Capanna R, Bertoni F, Bettelli G, Picci P, Bacchini P, Present D, Giunti A, Campanacci M (1988) Dedifferentiated chondrosarcoma. J Bone Jt Surg Am 70:60–69
12.
Casorzo L, Chiecchio L, Pisacane A, Fumero S, Canavese F, Torchio B, Risio M (2003) Cytogenetic findings in a case of dedifferentiated chondrosarcoma. Cancer Genet Cytogenet 144:61–64PubMedCrossRef
13.
Coughlan B, Feliz A, Ishida T, Czerniak B, Dorfman HD (1995) p53 expression and DNA ploidy of cartilage lesions. Human Pathol 26:620–624CrossRef
14.
15.
Dickey ID, Rose PS, Fuchs B, Wold LE, Okuno SH, Sim FH, Scully SP (2004) Dedifferentiated chondrosarcoma: the role of chemotherapy with updated outcomes. J Bone Jt Surg Am 86-A:2412–2418
16.
Dragoo JL, Samimi B, Zhu M, Hame SL, Thomas BJ, Lieberman JR, Hedrick MH, Benhaim P (2003) Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads. J Bone Jt Surg Br 85:740–747
17.
Frassica FJ, Unni KK, Beabout JW, Sim FH (1986) Dedifferentiated chondrosarcoma. A report of the clinicopathological features and treatment of seventy-eight cases. J Bone Jt Surg Am 68:1197–1205
18.
Gattenloehner S, Dockhorn-Dworniczak B, Leuschner I, Vincent A, Muller-Hermelink HK, Marx A (1999) A comparison of MyoD1 and fetal acetylcholine receptor expression in childhood tumors and normal tissues: implications for the molecular diagnosis of minimal disease in rhabdomyosarcomas. J Mol Diagn 1:23–31PubMed
19.
Gisselsson D, Palsson E, Hoglund M, Domanski H, Mertens F, Pandis N, Sciot R, Dal Cin P, Bridge JA, Mandahl N (2002) Differentially amplified chromosome 12 sequences in low- and high-grade osteosarcoma. Genes Chromosomes Cancer 33:133–140PubMedCrossRef
20.
Grote HJ, Schneider-Stock R, Neumann W, Roessner A (2000) Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma. Virchows Arch 436:494–497PubMedCrossRef
21.
Haberler C, Gelpi E, Marosi C, Rossler K, Birner P, Budka H, Hainfellner JA (2006) Immunohistochemical analysis of platelet-derived growth factor receptor-alpha, -beta, c-kit, c-abl, and arg proteins in glioblastoma: possible implications for patient selection for imatinib mesylate therapy. J Neuro-oncol 76:105–109CrossRef
22.
Hayami T, Shukunami C, Mitsui K, Endo N, Tokunaga K, Kondo J, Takahashi HE, Hiraki Y (1999) Specific loss of chondromodulin-I gene expression in chondrosarcoma and the suppression of tumor angiogenesis and growth by its recombinant protein in vivo. FEBS Lett 458:436–440PubMedCrossRef
23.
Holtkamp N, Okuducu AF, Mucha J, Afanasieva A, Hartmann C, Atallah I, Estevez-Schwarz L, Mawrin C, Friedrich RE, Mautner VF, Deimling A (2006) Mutation and expression of PDGFRA and KIT in malignant peripheral nerve sheath tumors, and its implications for imatinib sensitivity. Carcinogenesis 27:664–671PubMedCrossRef
24.
Hotta T, Motoyama T, Watanabe H (1992) Three human osteosarcoma cell lines exhibiting different phenotypic expressions. Acta Pathol Jpn 42:595–603PubMed
25.
Huang B, Ning Y, Lamb AN, Sandlin CJ, Jamehdor M, Ried T, Bartley J (1998) Identification of an unusual marker chromosome by spectral karyotyping. Am J Med Genet 80:368–372PubMedCrossRef
26.
Jaworski RC (1984) Dedifferentiated chondrosarcoma. An ultrastructural study. Cancer 53:2674–2678PubMedCrossRef
27.
Kahn LB (1976) Chondrosarcoma with dedifferentiated foci. A comparative and ultrastructural study. Cancer 37:1365–1375PubMedCrossRef
28.
Knuutila S, Armengol G, Bjorkqvist AM, el-Rifai W, Larramendy ML, Monni O, Szymanska J (1998) Comparative genomic hybridization study on pooled DNAs from tumors of one clinical–pathological entity. Cancer Genet Cytogenet 100:25–30PubMedCrossRef
29.
Kudawara I, Araki N, Myoui A, Kato Y, Uchida A, Yoshikawa H (2004) New cell lines with chondrocytic phenotypes from human chondrosarcoma. Virchows Arch 444:577–586PubMedCrossRef
30.
Kunisada T, Miyazaki M, Mihara K, Gao C, Kawai A, Inoue H, Namba M (1998) A new human chondrosarcoma cell line (OUMS-27) that maintains chondrocytic differentiation. Int J Cancer 77:854–859PubMedCrossRef
31.
Lagonigro MS, Tamborini E, Negri T, Staurengo S, Dagrada GP, Miselli F, Gabanti E, Greco A, Casali PG, Carbone A, Pierotti MA, Pilotti S (2006) PDGFRalpha, PDGFRbeta and KIT expression/activation in conventional chondrosarcoma. J Pathol 208:615–623PubMedCrossRef
32.
Lau CC, Harris CP, Lu XY, Perlaky L, Gogineni S, Chintagumpala M, Hicks J, Johnson ME, Davino NA, Huvos AG, Meyers PA, Healy JH, Gorlick R, Rao PH (2004) Frequent amplification and rearrangement of chromosomal bands 6p12–p21 and 17p11.2 in osteosarcoma. Genes Chromosomes Cancer 39:11–21PubMedCrossRef
33.
Larramendy ML, Mandahl N, Mertens F, Blomqvist C, Kivioja AH, Karaharju E, Valle J, Bohling T, Tarkkanen M, Rydholm A, Akerman M, Bauer HC, Anttila JP, Elomaa I, Knuutila S (1999) Clinical significance of genetic imbalances revealed by comparative genomic hybridization in chondrosarcomas. Human Pathol 30:1247–1253CrossRef
34.
Mandahl N, Gustafson P, Mertens F, Akerman M, Baldetorp B, Gisselsson D, Knuutila S, Bauer HC, Larsson O (2002) Cytogenetic aberrations and their prognostic impact in chondrosarcoma. Genes Chromosomes Cancer 33:188–200PubMedCrossRef
35.
McCarthy EF, Dorfman HD (1982) Chondrosarcoma of bone with dedifferentiation: a study of eighteen cases. Human Pathol 13:36–40CrossRef
36.
McFarland GB Jr, McKinley LM, Reed RJ (1977) Dedifferentiation of low grade chondrosarcomas. Clin Orthop Relat Res 122:157–164PubMed
37.
McGary EC, Onn A, Mills L, Heimberger A, Eton O, Thomas GW, Shtivelband M, Bar-Eli M (2004) Imatinib mesylate inhibits platelet-derived growth factor receptor phosphorylation of melanoma cells but does not affect tumorigenicity in vivo. J Invest Dermatol 122:400–405PubMedCrossRef
38.
McGary EC, Weber K, Mills L, Doucet M, Lewis V, Lev DC, Fidler IJ, Bar-Eli M (2002) Inhibition of platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571. Clin Cancer Res 8:3584–3591PubMed
39.
Merchant MS, Woo CW, Mackall CL, Thiele CJ (2002) Potential use of imatinib in Ewing’s Sarcoma: evidence for in vitro and in vivo activity. J Natl Cancer Inst 94:1673–1679PubMed
40.
Mirra JM, Marcove RC (1974) Fibrosarcomatous dedifferentiation of primary and secondary chondrosarcoma. Review of five cases. J Bone Jt Surg Am 56:285–296
41.
Mitchell AD, Ayoub K, Mangham DC, Grimer RJ, Carter SR, Tillman RM (2000) Experience in the treatment of dedifferentiated chondrosarcoma. J Bone Jt Surg Br 82:55–61CrossRef
42.
Mitelman F (1995) An international system for human cytogenetic nomenclature. Basel: S. Karger
43.
Nawa G, Ueda T, Mori S, Yoshikawa H, Fukuda H, Ishiguro S, Funai H, Uchida A (1996) Prognostic significance of Ki67 (MIB1) proliferation index and p53 over-expression in chondrosarcomas. Int J Cancer 69:86–91PubMedCrossRef
44.
O'Malley DP, Opheim KE, Barry TS, Chapman DB, Emond MJ, Conrad EU, Norwood TH (2001) Chromosomal changes in a dedifferentiated chondrosarcoma: a case report and review of the literature. Cancer Genet Cytogenet 124:105–111PubMedCrossRef
45.
Oshiro Y, Chaturvedi V, Hayden D, Nazeer T, Johnson M, Johnston DA, Ordonez NG, Ayala AG, Czerniak B (1998) Altered p53 is associated with aggressive behavior of chondrosarcoma: a long term follow-up study. Cancer 83:2324–2234PubMedCrossRef
46.
Ozisik YY, Meloni AM, Peier A, Altungoz O, Spanier SS, Zalupski MM, Leong SP, Sandberg AA (1994) Cytogenetic findings in 19 malignant bone tumors. Cancer 74:2268–2275PubMedCrossRef
47.
Sandberg AA, Bridge JA (2003) Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: chondrosarcoma and other cartilaginous neoplasms. Cancer Genet Cytogenet 143:1–31PubMedCrossRef
48.
Sato Y, Sasaki H, Kobayashi Y, Haruki N, Toyama T, Kondo S, Fujii Y (2003) Expression of PPAR-gamma is correlated with the clinical course of neuroblastoma. J Pediatr Surg 38:205–210PubMedCrossRef
49.
Sawyer JR, Swanson CM, Lukacs JL, Nicholas RW, North PE, Thomas JR (1998) Evidence of an association between 6q13–21 chromosome aberrations and locally aggressive behavior in patients with cartilage tumors. Cancer 82:474–483PubMedCrossRef
50.
Schrock E, Veldman T, Padilla-Nash H, Ning Y, Spurbeck J, Jalal S, Shaffer LG, Papenhausen P, Kozma C, Phelan MC, Kjeldsen E, Schonberg SA, O'Brien P, Biesecker L, Manoir S, Ried T (1997) Spectral karyotyping refines cytogenetic diagnostics of constitutional chromosomal abnormalities. Hum Genet 101:255–262PubMedCrossRef
51.
Seabright M (1971) A rapid banding technique for human chromosomes. Lancet 50:971–972CrossRef
52.
Shirahama S, Nakamura Y, Ogura K, Ishikawa H, Harima Y (1999) P53 gene analysis with Autosequencer. SRL Hokan 23:57–64
53.
Simms WW, Ordonez NG, Johnston D, Ayala AG, Czerniak B (1995) p53 expression in dedifferentiated chondrosarcoma. Cancer 76:223–227PubMedCrossRef
54.
Squire JA, Pei J, Marrano P, Beheshti B, Bayani J, Lim G, Moldovan L, Zielenska M (2003) High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays. Genes Chromosomes Cancer 38:215–225PubMedCrossRef
55.
Swarts SJ, Neff JR, Johansson SL, Bridge JA (1996) Cytogenetic analysis of dedifferentiated chondrosarcoma. Cancer Genet Cytogenet 89:49–51PubMedCrossRef
56.
Tarkkanen M, Elomaa I, Blomqvist C, Kivioja AH, Kellokumpu-Lehtinen P, Bohling T, Valle J, Knuutila S (1999) DNA sequence copy number increase at 8q: a potential new prognostic marker in high-grade osteosarcoma. Int J Cancer 84:114–121PubMedCrossRef
57.
Toguchida J, Yamaguchi T, Ritchie B, Beauchamp RL, Dayton SH, Herrera GE, Yamamuro T, Kotoura Y, Sasaki MS, Little JB, Weichselbaum RR, Ishizaki K, Yandell DW (1992) Mutation spectrum of the p53 gene in bone and soft tissue sarcomas. Cancer Res 52:6194–6199PubMed
58.
Veldman T, Vignon C, Schrock E, Rowley JD, Ried T (1997) Hidden chromosome abnormalities in haematological malignancies detected by multicolour spectral karyotyping. Nat Genet 15:406–410PubMedCrossRef
59.
Yagami K, Uyama Y, Yoshizawa Y, Kakuta S, Yamaguchi A, Nagumo M (2004) A human chondrogenic cell line retains multi-potency that differentiates into osteoblasts and adipocytes. Bone 34:648–655PubMedCrossRef
60.
Wadayama B, Toguchida J, Yamaguchi T, Sasaki MS, Yamamuro T (1993) p53 expression and its relationship to DNA alterations in bone and soft tissue sarcomas. Br J Cancer 68:1134–1139PubMed
61.
Wordinger RJ, Agarwal R, Talati M, Fuller J, Lambert W, Clark AF (2002) Expression of bone morphogenetic proteins (BMP), BMP receptors, and BMP associated proteins in human trabecular meshwork and optic nerve head cells and tissues. Mol Vis 8:241–250PubMed
62.
Zalupski MM, Ensley JF, Ryan J, Selvaggi S, aker LH, Wolman SR (1990) A common cytogenetic abnormality and DNA content alterations in dedifferentiated chondrosarcoma. Cancer 66:1176–1182PubMedCrossRef
63.
Zielenska M, Bayani J, Pandita A, Toledo S, Marrano P, Andrade J, Petrilli A, Thorner P, Sorensen P, Squire JA (2001) Comparative genomic hybridization analysis identifies gains of 1p35 approximately p36 and chromosome 19 in osteosarcoma. Cancer Genet Cytogenet 130:14–21PubMedCrossRef
Metadata
Title
Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation
Authors
Naoko Kudo
Akira Ogose
Tetsuo Hotta
Hiroyuki Kawashima
Wenguang Gu
Hajime Umezu
Tsuyoshi Toyama
Naoto Endo
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 3/2007
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-007-0426-3

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