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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

AXL is a potential therapeutic target in dedifferentiated and pleomorphic liposarcomas

Authors: Caitlin D. May, Jeannine Garnett, XiaoYan Ma, Sharon M. Landers, Davis R. Ingram, Elizabeth G. Demicco, Ghadah A. Al Sannaa, Tona Vu, Lixia Han, Yi Zhang, Christine M. Kivlin, Svetlana Bolshakov, Azad Abul Kalam, Juehui Liu, Fuguo Zhou, Dominique Broccoli, Wei-Lien Wang, Alexander J. Lazar, Raphael E. Pollock, Dina Lev, Keila E. Torres

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

AXL is a well-characterized, protumorigenic receptor tyrosine kinase that is highly expressed and activated in numerous human carcinomas and sarcomas, including aggressive subtypes of liposarcoma. However, the role of AXL in the pathogenesis of well-differentiated (WDLPS), dedifferentiated (DDLPS), and pleomorphic liposarcoma (PLS) has not yet been determined.

Methods

Immunohistochemical analysis of AXL expression was conducted on two tissue microarrays containing patient WDLPS, DDLPS, and PLS samples. A panel of DDLPS and PLS cell lines were interrogated via western blot for AXL expression and activity and by ELISA for growth arrest-specific 6 (GAS6) production. AXL knockdown was achieved by siRNA or shRNA. The effects of AXL knockdown on cell proliferation, migration, and invasion were measured in vitro. In addition, AXL shRNA-containing DDLPS cells were assessed for their tumor-forming capacity in vivo.

Results

In this study, we determined that AXL is expressed in a subset of WDLPS, DDLPS, and PLS patient tumor samples. In addition, AXL and its ligand GAS6 are expressed in a panel of DDLPS and PLS cell lines. We show that the in vitro activation of AXL via stimulation with exogenous GAS6 resulted in a significant increase in cell proliferation, migration, and invasion in DDLPS and PLS cell lines. Transient knockdown of AXL resulted in attenuation of these protumorigenic phenotypes in vitro. Stable AXL knockdown not only decreased migratory and invasive characteristics of DDLPS and PLS cells in vitro but also significantly diminished tumorigenicity of two dedifferentiated liposarcoma xenograft models in vivo.

Conclusions

Our results suggest that AXL signaling contributes to the aggressiveness of DDLPS and PLS, and that AXL is therefore a potential therapeutic target for treatment of these rare, yet devastating tumors.
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Metadata
Title
AXL is a potential therapeutic target in dedifferentiated and pleomorphic liposarcomas
Authors
Caitlin D. May
Jeannine Garnett
XiaoYan Ma
Sharon M. Landers
Davis R. Ingram
Elizabeth G. Demicco
Ghadah A. Al Sannaa
Tona Vu
Lixia Han
Yi Zhang
Christine M. Kivlin
Svetlana Bolshakov
Azad Abul Kalam
Juehui Liu
Fuguo Zhou
Dominique Broccoli
Wei-Lien Wang
Alexander J. Lazar
Raphael E. Pollock
Dina Lev
Keila E. Torres
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1916-3

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