Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment

Mary E Vail1, Carmel Murone2, April Tan3

  • 1Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia. mary.vail@monash.edu Andrew.Scott@ludwig.edu.au Martin.Lackmann@monash.edu.

Cancer Research
|August 16, 2014
PubMed

Insights

EphA3, a receptor tyrosine kinase, is unexpectedly overexpressed in human cancers. Its activation inhibits tumor growth by disrupting the tumor microenvironment, suggesting EphA3 agonists as a novel anticancer therapy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Eph receptor tyrosine kinases (RTKs) are crucial for cell communication in tissue development and cancer.
  • While some cancer genomes suggest EphA3 acts as a tumor suppressor, its role in oncogenesis is unclear.
  • The expression patterns of EphA3 in tumors are not well understood.

Purpose of the Study:

  • To investigate the expression pattern and function of EphA3 in the tumor microenvironment.
  • To determine the therapeutic potential of targeting EphA3 in cancer.

Main Methods:

  • Analysis of EphA3 expression in human cancers and mouse tumor xenografts.
  • In vitro studies on EphA3 activation in mesenchymal/stromal cells.
  • In vivo studies using agonistic α-EphA3 antibodies in mice.

Main Results:

  • EphA3 is unexpectedly overexpressed in the tumor microenvironment of various cancers.
  • Activation of EphA3 on mesenchymal/stromal cells induces cell contraction, segregation, and apoptosis.
  • Treatment with an EphA3 agonist disrupts tumor stroma and microvasculature integrity, inhibiting tumor growth.

Conclusions:

  • EphA3 is a novel target for selectively eliminating the tumor microenvironment.
  • EphA3 agonists show potential as an anticancer therapeutic strategy.

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