Establishment and characterization of two distinct malignant mesothelioma cell lines with common clonal origin

      Abstract

      We describe two newly established malignant mesothelioma (MM) cell lines derived from a pleural effusion of a male. One cell line, designated as MM-Z03E, reveals an epithelioid cobblestone morphology, while the second one, designated as MM-Z03S and subcloned after in vivo selection, exhibits a sarcomatoid storiform growth pattern. Both cell lines showed the immunologic profile characteristic for MM (i.e., expression of cytokeratin, CK18, calretinin, and vimentin in both phenotypes). Cytogenetics, multicolor fluorescence in situ hybridization, comparative genomic hybridization, and oligonucleotide array CGH were performed on both cell lines. Aberrations shared by both cell lines included chromosomal losses of 1q34∼qter, 4, 9p, 10p, 13, 14, 16q, 18, and 22, as well as a complex structural aberration involving chromosome 17. Aberrations exclusive to MM-Z03E included gains of 3q11q27 and 5p, while gain of 9q and losses of 3q27qter, 11q, and 18 in MM-Z03S were exclusive to MM-Z03E. Both cell lines were able to develop solid transplant tumors in nude mice within 16 weeks, and immunophenotyping of tumor xenografts revealed an overall retained expression profile of the markers used. Remarkably, one xenograft from MM-Z03E revealed overexpression of p53 and widely invasive growth. In conclusion, both cell lines are useful in vivo and in vitro model systems to study the underlying genetic mechanisms of biphasic differentiation in MM, which can be of certain value considering the increasing relevance of assessing MM tumor biology for the clinical management of this disease.
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      References

      1. Travis W.D. Brambilla E. Müller-Hermelink H.K. Harris C.C. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. IARC Press, . Lyon2004
        • Simon F.
        • Johnen G.
        • Krismann M.
        • Muller K.M.
        Chromosomal alterations in early stages of malignant mesotheliomas.
        Virchows Arch. 2005; 447: 762-767
        • Ceresoli G.L.
        • Zucali P.A.
        • Favaretto A.G.
        • Grossi F.
        • Bidoli P.
        • Del Conte G.
        • Ceribelli A.
        • Bearz A.
        • Morenghi E.
        • Cavina R.
        • Marangolo M.
        • Parra H.J.
        • Santoro A.
        Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma.
        J Clin Oncol. 2006; 24: 1443-1448
        • Gordon G.J.
        • Rockwell G.N.
        • Godfrey P.A.
        • Jensen R.V.
        • Glickman J.N.
        • Yeap B.Y.
        • Richards W.G.
        • Sugarbaker D.J.
        • Bueno R.
        Validation of genomics-based prognostic tests in malignant pleural mesothelioma.
        Clin Cancer Res. 2005; 11: 4406-4414
        • Kindler H.L.
        • Vogelzang N.
        Mesothelioma.
        in: Vokes E.E. Golomb H. Oncologic therapies. Springer-Verlag, Berlin2003: 415-423
        • Johansson L.
        • Linden C.J.
        Aspects of histopathologic subtype as a prognostic factor in 85 pleural mesotheliomas.
        Chest. 1996; 109: 109-114
        • Shaffer L.G.
        • Tommerup N.
        ISCN 2005: An International System for Human Cytogenetic Nomenclature.
        S. Karger, Basel2005
        • Gunawan B.
        • Schulten H.J.
        • von Heydebreck A.
        • Schmidt B.
        • Enders C.
        • Hoer J.
        • Langer C.
        • Schuler P.
        • Schindler C.G.
        • Kuhlgatz J.
        • Füzesi L.
        Site-independent prognostic value of chromosome 9q loss in primary gastrointestinal stromal tumours.
        J Pathol. 2004; 202: 421-429
        • Kivipensas P.
        • Bjorkqvist A.M.
        • Karhu R.
        • Pelin K.
        • Linnainmaa K.
        • Tammilehto L.
        • Mattson K.
        • Kallioniemi Q.P.
        • Knuutila S.
        Gains and losses of DNA sequences in malignant mesothelioma by comparative genomic hybridization.
        Cancer Genet Cytogenet. 1996; 89: 7-13
        • Ruco L.P.
        • de Laat P.A.
        • Matteucci C.
        • Bernasconi S.
        • Sciacca F.M.
        • van der Kwast T.H.
        • Hoogsteden H.C.
        • Uccini S.
        • Mantovani A.
        • Versnel M.A.
        Expression of ICAM-1 and VCAM-1 in human malignant mesothelioma.
        J Pathol. 1996; 179: 266-271
        • Philippeaux M.M.
        • Pache J.C.
        • Dahoun S.
        • Barnet M.
        • Robert J.H.
        • Mauel J.
        • Spiliopoulos A.
        Establishment of permanent cell lines purified from human mesothelioma: morphological aspects, new marker expression and karyotypic analysis.
        Histochem Cell Biol. 2004; 122: 249-260
        • Kumar K.
        • Rahman Q.
        • Schipper H.
        • Matschegewski C.
        • Schiffmann D.
        • Papp T.
        Mutational analysis of 9 different tumour-associated genes in human malignant mesothelioma cell lines.
        Oncol Rep. 2005; 14: 743-750
        • Reale F.R.
        • Griffin T.W.
        • Compton J.M.
        • Graham S.
        • Townes P.L.
        • Bogden A.
        Characterization of a human malignant mesothelioma cell line (H-MESO-1): a biphasic solid and ascitic tumor model.
        Cancer Res. 1987; 47: 3199-3205
        • Sun X.
        • Dobra K.
        • Bjornstedt M.
        • Hjerpe A.
        Upregulation of 9 genes, including that for thioredoxin, during epithelial differentiation of mesothelioma cells.
        Differentiation. 2000; 66: 181-188
        • Usami N.
        • Fukui T.
        • Kondo M.
        • Taniguchi T.
        • Yokoyama T.
        • Mori S.
        • Yokoi K.
        • Horio Y.
        • Shimokata K.
        • Sekido Y.
        • Hida T.
        Establishment and characterization of four malignant pleural mesothelioma cell lines from Japanese patients.
        Cancer Sci. 2006; 97: 387-394
        • Klominek J.
        • Robert K.H.
        • Hjerpe A.
        • Wickstrom B.
        • Gahrton G.
        Serum-dependent growth patterns of two, newly established human mesothelioma cell lines.
        Cancer Res. 1989; 49: 6118-6122
        • Bjorkqvist A.M.
        • Tammilehto L.
        • Anttila S.
        • Mattson K.
        • Knuutila S.
        Recurrent DNA copy number changes in 1q, 4q, 6q, 9p, 13q, 14q and 22q detected by comparative genomic hybridization in malignant mesothelioma.
        Br J Cancer. 1997; 75: 523-527
        • Krismann M.
        • Muller K.M.
        • Jaworska M.
        • Johnen G.
        Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas: DNA cytometry and comparative genomic hybridization of 90 cases.
        J Pathol. 2002; 197: 363-371
        • Cheng J.Q.
        • Jhanwar S.C.
        • Lu Y.Y.
        • Testa J.R.
        Homozygous deletions within 9p21-p22 identify a small critical region of chromosomal loss in human malignant mesotheliomas.
        Cancer Res. 1993; 53: 4761-4763
        • Nagel H.
        • Schulten H.J.
        • Gunawan B.
        • Brinck U.
        • Füzesi L.
        The potential value of comparative genomic hybridization analysis in effusion-and fine needle aspiration cytology.
        Mod Pathol. 2002; 15: 818-825
        • Illei P.B.
        • Rusch V.W.
        • Zakowski M.F.
        • Ladanyi M.
        Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas.
        Clin Cancer Res. 2003; 9: 2108-2113
        • Pelin-Enlund K.
        • Husgafvel-Pursiainen K.
        • Tammilehto L.
        • Klockars M.
        • Jantunen K.
        • Gerwin B.I.
        • Harris C.C.
        • Tuomi T.
        • Vanhala E.
        • Mattson K.
        • Linnainmaa K.
        Asbestos-related malignant mesothelioma: growth, cytology, tumorigenicity and consistent chromosome findings in cell lines from five patients.
        Carcinogenesis. 1990; 11: 673-681
        • Knuuttila A.
        • Jee K.J.
        • Taskinen E.
        • Wolff H.
        • Knuutila S.
        • Anttila S.
        Spindle cell tumours of the pleura: a clinical, histological and comparative genomic hybridization analysis of 14 cases.
        Virchows Arch. 2006; 448: 135-141
        • Metcalf R.A.
        • Welsh J.A.
        • Bennett W.P.
        • Seddon M.B.
        • Lehman T.A.
        • Pelin K.
        • Linnainmaa K.
        • Tammilehto L.
        • Mattson K.
        • Gerwin B.I.
        • Harris C.C.
        p53 and Kirsten-ras mutations in human mesothelioma cell lines.
        Cancer Res. 1992; 52: 2610-2615
        • Cheng J.Q.
        • Lee W.C.
        • Klein M.A.
        • Cheng G.Z.
        • Jhanwar S.C.
        • Testa J.R.
        Frequent mutations of NF2 and allelic loss from chromosome band 22q12 in malignant mesothelioma: evidence for a two-hit mechanism of NF2 inactivation.
        Genes Chromosomes Cancer. 1999; 24: 238-242