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.
Liposarcoma Peritoneal sarcomatosis WDLPS DDLPS Cell culture model
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We would like to thank Dr. Dina Lev (MD Anderson Cancer Center) for providing us cell lines Lipo246 and PLS-1. The study was supported in part by a grant from the Deutsche Forschungsgemeinschaft (KR 3496/2-1 to Andreas Krieg).
Compliance with ethical standards
This study was funded by the Deutsche Forschungsgemeinschaft (KR 3496/2-1).
Conflicts of interest
Statement of human rights
Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Statement on the welfare of animals
Ethical approval: All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Informed consent was obtained from all individual participants included in the study.
Supplementary Fig. 1Copy number gains of commonly altered oncogenes in DDLPS. A detailed view on region 12q14.1-15 displayed typical oncogenic alterations of DDLPS in the adipocytic (C1; red area) or leiomyomatous (C2; blue area) component of the primary tumor, peritoneal sarcomatosis (PS; green area) and Lipo-DUE1 cells (CL; grey area). (A) TSPAN-31, CDK4 and AVIL on 12q14.1, (B) HMGA2 on 12q14.3 and (C) MDM2 on 12q15. Evaluation was done by ADM-2 algorithm with a threshold of 6.0. (PPT 528 kb)
Supplementary Fig. 2Copy number gain of C-MYC. Detailed view of aCGH profiles identifying copy number alterations for C-MYC on 12q24.21 in the leiomyomatous (C2; blue area) component of the primary tumor, peritoneal sarcomatosis (PS; green area) and Lipo-DUE1 cells (CL; grey area). The adipocytic (C1) differentiated area of the primary LPS exhibited a normal C-MYC gene copy number (absence of a colored area in the aCGH profile). Evaluation was done by ADM-2 algorithm with a threshold of 6.0. (PPT 151 kb)
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