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15.09.2015 | Original Article

Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma

verfasst von: Sabrina Mersch, Jasmin C. Riemer, Philipp M. Schlünder, Markus P. Ghadimi, Hany Ashmawy, Birte Möhlendick, Stefan A. Topp, Tanja Arent, Patric Kröpil, Nikolas H. Stoecklein, Helmut E. Gabbert, Wolfram T. Knoefel, Andreas Krieg

Erschienen in: Tumor Biology | Ausgabe 2/2016

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Abstract

Approximately 50–70 % of patients with retroperitoneal or intraabdominal sarcoma develop a relapse after surgical therapy, including peritoneal sarcomatosis, an extremely rare site of metastatic disease which is associated with an extremely poor prognosis. Accordingly, the establishment of a permanent cell line derived from peritoneal sarcomatosis might provide a helpful tool to understand the biological behavior and to develop new therapeutic strategies. Thus, we established and characterized a liposarcoma cell line (Lipo-DUE1) from a peritoneal sarcomatosis that was permanently cultured without showing any morphological changes. Lipo-DUE1 cells exhibited a spindle-shaped morphology and positive staining for S100. Tumorigenicity was demonstrated in vitro by invasion and migration assays and in vivo by using a subcutaneous xenograft mouse model. In addition, aCGH analysis revealed concordant copy number variations on chromosome 12q in the primary tumor, peritoneal sarcomatosis, and Lipo-DUE1 cells that are commonly observed in liposarcoma. Chemotherapeutic sensitivity assays revealed a pronounced drug-resistant phenotype of Lipo-DUE1 cells to conventionally used chemotherapeutic agents. In conclusion, we describe for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies.

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Mack TM. Sarcomas and other malignancies of soft tissue, retroperitoneum, peritoneum, pleura, heart, mediastinum, and spleen. Cancer. 1995;75(1 Suppl):211–44.CrossRefPubMed

Dei Tos AP. Liposarcoma: new entities and evolving concepts. Ann Diagn Pathol. 2000;4(4):252–66.CrossRefPubMed

Crago AM, Singer S. Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma. Curr Opin Oncol. 2011;23(4):373–8.CrossRefPubMedPubMedCentral

Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. WHO classifica tion of tumours of soft tissue and bone. 4th ed. WHO classifica tion of tumours of soft tissue and bone. Lyon: International Agency for Research on Cancer (IACR); 2013.

Singer S, Antonescu CR, Riedel E, Brennan MF. Histologic subtype and margin of resection predict pattern of recurrence and survival for retroperitoneal liposarcoma. Ann Surg. 2003;238(3):358–70. discussion 70-1.PubMedPubMedCentral

Fabre-Guillevin E, Coindre JM, Somerhausen Nde S, Bonichon F, Stoeckle E, Bui NB. Retroperitoneal liposarcomas: follow-up analysis of dedifferentiation after clinicopathologic reexamination of 86 liposarcomas and malignant fibrous histiocytomas. Cancer. 2006;106(12):2725–33.CrossRefPubMed

Stojadinovic A, Leung DH, Hoos A, Jaques DP, Lewis JJ, Brennan MF. Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas. Ann Surg. 2002;235(3):424–34.CrossRefPubMedPubMedCentral

Stefanovski PD, Bidoli E, De Paoli A, Buonadonna A, Boz G, Libra M, et al. Prognostic factors in soft tissue sarcomas: a study of 395 patients. Eur J Surg Oncol. 2002;28(2):153–64.CrossRefPubMed

Hoffman A, Lazar AJ, Pollock RE, Lev D. New frontiers in the treatment of liposarcoma, a therapeutically resistant malignant cohort. Drug Resist Updat. 2011;14(1):52–66.CrossRefPubMed

10.

Rosai J, Akerman M, Dal Cin P, DeWever I, Fletcher CD, Mandahl N, et al. Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP study group). Am J Surg Pathol. 1996;20(10):1182–9.CrossRefPubMed

11.

Pedeutour F, Suijkerbuijk RF, Forus A, Van Gaal J, Van de Klundert W, Coindre JM, et al. Complex composition and co-amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcoma. Genes Chromosomes Cancer. 1994;10(2):85–94.CrossRefPubMed

12.

Pedeutour F, Forus A, Coindre JM, Berner JM, Nicolo G, Michiels JF, et al. Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer. 1999;24(1):30–41.CrossRefPubMed

13.

Rieker RJ, Weitz J, Lehner B, Egerer G, Mueller A, Kasper B, et al. Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways. Virchows Arch. 2010;456(3):277–85.CrossRefPubMed

14.

Dei Tos AP, Doglioni C, Piccinin S, Sciot R, Furlanetto A, Boiocchi M, et al. Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours. J Pathol. 2000;190(5):531–6.CrossRefPubMed

15.

Conyers R, Young S, Thomas DM. Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.CrossRefPubMed

16.

Issels RD, Abdel-Rahman S, Wendtner C, Falk MH, Kurze V, Sauer H, et al. Neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for locally advanced primary or recurrent high-risk adult soft-tissue sarcomas (STS) of adults: long-term results of a phase II study. Eur J Cancer. 2001;37(13):1599–608.CrossRefPubMed

17.

Schmitt T, Lehner B, Kasper B, Bischof M, Roeder F, Dietrich S, et al. A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma. BMC Cancer. 2011;11:510.CrossRefPubMedPubMedCentral

18.

Adjuvant chemotherapy for localised resectable soft tissue sarcoma in adults. Sarcoma meta-analysis collaboration (SMAC). Cochrane Database Syst Rev. 2000(2):CD001419.

19.

Bilimoria MM, Holtz DJ, Mirza NQ, Feig BW, Pisters PW, Patel S, et al. Tumor volume as a prognostic factor for sarcomatosis. Cancer. 2002;94(9):2441–6.CrossRefPubMed

20.

Salti GI, Ailabouni L, Undevia S. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal sarcomatosis. Ann Surg Oncol. 2012;19(5):1410–5.CrossRefPubMed

21.

Randle RW, Swett KR, Shen P, Stewart JH, Levine EA, Votanopoulos KI. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in peritoneal sarcomatosis. Am Surg. 2013;79(6):620–4.PubMedPubMedCentral

22.

Dalal KM, Kattan MW, Antonescu CR, Brennan MF, Singer S. Subtype specific prognostic nomogram for patients with primary liposarcoma of the retroperitoneum, extremity, or trunk. Ann Surg. 2006;244(3):381–91.PubMedPubMedCentral

23.

Peng T, Zhang P, Liu J, Nguyen T, Bolshakov S, Belousov R, et al. An experimental model for the study of well-differentiated and dedifferentiated liposarcoma; deregulation of targetable tyrosine kinase receptors. Lab Investig. 2011;91(3):392–403.CrossRefPubMed

24.

Stratford EW, Castro R, Daffinrud J, Skarn M, Lauvrak S, Munthe E, et al. Characterization of liposarcoma cell lines for preclinical and biological studies. Sarcoma. 2012;2012:148614.CrossRefPubMedPubMedCentral

25.

Lahat G, Zhu QS, Huang KL, Wang S, Bolshakov S, Liu J, et al. Vimentin is a novel anti-cancer therapeutic target; insights from in vitro and in vivo mice xenograft studies. PLoS One. 2010;5(4):e10105.CrossRefPubMedPubMedCentral

26.

Kiguchi K, Ishiwata I, Ishiwata E, Koshitaka Y, Ohara T, Okudai Y, et al. Establishment and characterization of a human liposarcoma cell line (HTLS) from the retroperitoneal liposarcoma. Hum Cell. 2005;18(1):45–52.CrossRefPubMed

27.

Krieg A, Mersch S, Boeck I, Dizdar L, Weihe E, Hilal Z, et al. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines. PLoS One. 2014;9(2):e88713.CrossRefPubMedPubMedCentral

28.

Mohlendick B, Stoecklein NH. Analysis of copy-number alterations in single cells using microarray-based comparative genomic hybridization (aCGH). Curr Protoc Cell Biol. 2014;65:22 19 1–22 19 23.CrossRef

29.

Trojani M, Contesso G, Coindre JM, Rouesse J, Bui NB, de Mascarel A, et al. Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer. 1984;33(1):37–42.CrossRefPubMed

30.

Wibmer C, Leithner A, Zielonke N, Sperl M, Windhager R. Increasing incidence rates of soft tissue sarcomas? A population-based epidemiologic study and literature review. Ann Oncol: Off J Eur Soc Med Oncol/ ESMO. 2010;21(5):1106–11. doi:10.1093/annonc/mdp415.CrossRef

31.

Fogh J, Wright WC, Loveless JD. Absence of HeLa cell contamination in 169 cell lines derived from human tumors. J Natl Cancer Inst. 1977;58(2):209–14.CrossRefPubMed

32.

Binh MB, Sastre-Garau X, Guillou L, de Pinieux G, Terrier P, Lagace R, et al. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surg Pathol. 2005;29(10):1340–7.CrossRefPubMed

33.

Jain M, Arvanitis C, Chu K, Dewey W, Leonhardt E, Trinh M, et al. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science. 2002;297(5578):102–4.CrossRefPubMed

34.

Tran D, Verma K, Ward K, Diaz D, Kataria E, Torabi A, et al. Functional genomics analysis reveals a MYC signature associated with a poor clinical prognosis in liposarcomas. Am J Pathol. 2015;185(3):717–28.CrossRefPubMed

Titel: Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma
verfasst von: Sabrina Mersch
Jasmin C. Riemer
Philipp M. Schlünder
Markus P. Ghadimi
Hany Ashmawy
Birte Möhlendick
Stefan A. Topp
Tanja Arent
Patric Kröpil
Nikolas H. Stoecklein
Helmut E. Gabbert
Wolfram T. Knoefel
Andreas Krieg
Publikationsdatum: 15.09.2015
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 2/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4050-6

Springer Medizin

Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma

Abstract

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Abstract

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