Universität zu Köln

Kuenstlinger, Helen, Fassunke, Jana, Schildhaus, Hans-Ulrich, Brors, Benedikt ORCID: 0000-0001-5940-3101, Heydt, Carina, Ihle, Michaela Angelika, Mechtersheimer, Gunhild, Wardelmann, Eva, Buettner, Reinhard and Merkelbach-Bruse, Sabine (2015). FGFR2 is overexpressed in myxoid liposarcoma and inhibition of FGFR signaling impairs tumor growth in vitro. Oncotarget, 6 (24). S. 20215 - 20231. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Myxoid liposarcomas account for more than one third of liposarcomas and about 10% of all adult soft tissue sarcomas. The tumors are characterized by specific chromosomal translocations leading to the chimeric oncogenes FUS-DDIT3 or EWS1R-DDIT3. The encoded fusion proteins act as aberrant transcription factors. Therefore, we implemented comparative expression analyses using whole-genome microarrays in tumor and fat tissue samples. We aimed at identifying differentially expressed genes which may serve as diagnostic or prognostic biomarkers or as therapeutic targets. Microarray analyses revealed overexpression of FGFR2 and other members of the FGF/FGFR family. Overexpression of FGFR2 was validated by qPCR, immunohistochemistry and western blot analysis in primary tumor samples. Treatment of the myxoid liposarcoma cell lines MLS 402 and MLS 1765 with the FGFR inhibitors PD173074, TKI258 (dovitinib) and BGJ398 as well as specific siRNAs reduced cell proliferation, induced apoptosis and delayed cell migration. Combination of FGFR inhibitors with trabectedin further increased the effect. Our study demonstrates overexpression of FGFR2 and a functional role of FGFR signaling in myxoid liposarcoma. As FGFR inhibition showed effects on proliferation and cell migration and induced apoptosis in vitro, our data indicate the potential use of FGFR inhibitors as a targeted therapy for these tumors.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kuenstlinger, Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED Fassunke, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Schildhaus, Hans-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Brors, Benedikt UNSPECIFIED orcid.org/0000-0001-5940-3101 UNSPECIFIED Heydt, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ihle, Michaela Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED Mechtersheimer, Gunhild UNSPECIFIED UNSPECIFIED UNSPECIFIED Wardelmann, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-396238
Journal or Publication Title:	Oncotarget
Volume:	6
Number:	24
Page Range:	S. 20215 - 20231
Date:	2015
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SOFT-TISSUE SARCOMAS; TIME RT-PCR; GENE-EXPRESSION; THERAPEUTIC TARGETS; SELECTIVE INHIBITOR; CHOP; FUSION; IDENTIFICATION; MUTATIONS; PATHWAY Multiple languages Oncology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39623