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Targeting Tie-2/angiopoietin axis in experimental mesothelioma confers differential responses and raises predictive

Sophia Magkouta1, Apostolos Pappas1, Ioannis S Pateras2

  • 1Marianthi Simou Laboratory, 1st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, Athens, 10675, Greece.

Oncotarget
|May 19, 2018
PubMed

Insights

A soluble angiopoietin inhibitor halted mesothelioma progression in mouse models by reducing tumor growth and angiogenesis. This therapeutic strategy shows promise for treating malignant pleural mesothelioma.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Malignant pleural mesothelioma is a challenging cancer with limited treatment options.
  • The angiopoietin/Tie-2 signaling pathway promotes mesothelioma cell growth.
  • Targeting this axis offers a potential therapeutic strategy.

Purpose of the Study:

  • To investigate the efficacy of a soluble angiopoietin inhibitor, Murine Tek-deltaFc, against malignant pleural mesothelioma in vivo.
  • To determine if inhibiting the angiopoietin/Tie-2 axis halts tumor progression by affecting cell proliferation and angiogenesis.
  • To identify potential biomarkers predicting response to this therapy.

Main Methods:

  • Two syngeneic mesothelioma mouse models (AB1 and AE17) were used.
  • Mice were treated with Murine Tek-deltaFc, a soluble angiopoietin inhibitor.
  • Tumor growth, apoptosis, and angiogenesis were assessed. Angiopoietin and Tie-2 expression levels were analyzed in tumors and patient samples.

Main Results:

  • Murine Tek-deltaFc significantly hampered AB1 mesothelioma growth in vivo, but not AE17.
  • The inhibitor enhanced tumor cell apoptosis and limited tumor angiogenesis in the responsive AB1 model.
  • Angiopoietins-1 and -2, and the inhibitor did not affect mesothelioma cell growth in vitro. Higher vascularity, endothelial Tie-2, and lower tumor Ang-1 expression predicted response.

Conclusions:

  • Disrupting the angiopoietin-Tie-2 signaling pathway can limit mesothelioma angiogenesis and halt tumor progression.
  • Tumor vascularity, endothelial Tie-2 expression, and tumor Ang-1 expression may predict mesothelioma response to Tek-deltaFc.
  • The angiopoietin/Tie-2 axis represents a viable therapeutic target for malignant pleural mesothelioma.
Keywords:
Tie-2angiopoietinsmalignant pleural mesotheliomamurine Tek-delta Fctumor angiogenesis

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