Related Experiment Video
Updated: Mar 30, 2026
Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
Published on: June 13, 2019
AXL is a potential therapeutic target in dedifferentiated and pleomorphic liposarcomas
Caitlin D May1,2, Jeannine Garnett3, XiaoYan Ma4
1Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. caitlin.d.may@gmail.com.
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.
Insights
AXL receptor tyrosine kinase signaling drives aggressive liposarcoma growth and metastasis. Targeting AXL may offer a new therapeutic strategy for dedifferentiated and pleomorphic liposarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- AXL is a protumorigenic receptor tyrosine kinase implicated in various carcinomas and sarcomas.
- Its role in well-differentiated (WDLPS), dedifferentiated (DDLPS), and pleomorphic liposarcoma (PLS) remains unclear.
- Understanding AXL's function is crucial for developing targeted therapies for aggressive liposarcoma subtypes.
Purpose of the Study:
- To investigate the expression and role of AXL in the pathogenesis of WDLPS, DDLPS, and PLS.
- To determine if AXL signaling contributes to the aggressive phenotypes of these liposarcoma subtypes.
- To evaluate AXL as a potential therapeutic target for liposarcoma treatment.
Main Methods:
- Immunohistochemical analysis of AXL expression in patient-derived WDLPS, DDLPS, and PLS samples.
- Western blot and ELISA to assess AXL expression, activity, and GAS6 production in liposarcoma cell lines.
- In vitro and in vivo studies using siRNA/shRNA to evaluate the effects of AXL knockdown on cell proliferation, migration, invasion, and tumorigenicity.
Main Results:
- AXL is expressed in a subset of WDLPS, DDLPS, and PLS tumors and in DDLPS/PLS cell lines along with its ligand GAS6.
- AXL activation by GAS6 significantly increased proliferation, migration, and invasion of DDLPS and PLS cells in vitro.
- AXL knockdown attenuated protumorigenic phenotypes in vitro and significantly diminished tumor formation in vivo.
Conclusions:
- AXL signaling contributes to the aggressiveness of dedifferentiated and pleomorphic liposarcoma.
- AXL represents a promising therapeutic target for treating these aggressive liposarcoma subtypes.
- Further investigation into AXL-targeted therapies is warranted for rare and devastating liposarcomas.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:23Abnormal Proliferation