Title |
Targeting EphA3 Inhibits Cancer Growth by Disrupting the Tumor Stromal Microenvironment
|
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Published in |
Cancer Research, August 2014
|
DOI | 10.1158/0008-5472.can-14-0218 |
Pubmed ID | |
Authors |
Mary E. Vail, Carmel Murone, April Tan, Linda Hii, Degu Abebe, Peter W. Janes, Fook-Thean Lee, Mark Baer, Varghese Palath, Christopher Bebbington, Geoffrey Yarranton, Carmen Llerena, Slavisa Garic, David Abramson, Glenn Cartwright, Andrew M. Scott, Martin Lackmann |
Abstract |
Eph receptor tyrosine kinases are critical for cell-cell communication during normal and oncogenic tissue patterning and tumor growth. Somatic mutation profiles of several cancer genomes suggest EphA3 as a tumor suppressor, but its oncogenic expression pattern and role in tumorigenesis remain largely undefined. Here, we report unexpected EphA3 overexpression within the microenvironment of a range of human cancers and mouse tumor xenografts where its activation inhibits tumor growth. EphA3 is found on mouse bone marrow-derived cells with mesenchymal and myeloid phenotypes, and activation of EphA3(+)/CD90(+)/Sca1(+) mesenchymal/stromal cells with an EphA3 agonist leads to cell contraction, cell-cell segregation, and apoptosis. Treatment of mice with an agonistic α-EphA3 antibody inhibits tumor growth by severely disrupting the integrity and function of newly formed tumor stroma and microvasculature. Our data define EphA3 as a novel target for selective ablation of the tumor microenvironment and demonstrate the potential of EphA3 agonists for anticancer therapy. Cancer Res; 74(16); 4470-81. ©2014 AACR. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 50% |
Canada | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 4% |
United States | 1 | 2% |
Germany | 1 | 2% |
Unknown | 50 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 14 | 26% |
Researcher | 13 | 24% |
Student > Bachelor | 7 | 13% |
Professor | 3 | 6% |
Other | 3 | 6% |
Other | 11 | 20% |
Unknown | 3 | 6% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 16 | 30% |
Medicine and Dentistry | 13 | 24% |
Biochemistry, Genetics and Molecular Biology | 9 | 17% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 7% |
Immunology and Microbiology | 2 | 4% |
Other | 4 | 7% |
Unknown | 6 | 11% |