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

Oncotarget
Sophia MagkoutaIoannis Kalomenidis

Abstract

Malignant pleural mesothelioma is resistant to currently used treatment. Angiopoieitn-1 directly promotes mesothelioma cell growth in a Tie-2-dependent fashion. Angiopoietin/Tie-2 axis may thus be valid targets for therapeutic interventions against mesothelioma. We hypothesized that a soluble angiopoietin inhibitor (Murine Tek-deltaFc) would halt mesothelioma progression in vivo by enhancing mesothelioma cell proliferation and inhibiting tumor angiogenesis. Our hypothesis was challenged on two syngeneic mesothelioma in vivo models (AB1 cells-Balb/c mice and AE17 cells-C57BL/6 mice. Even though both mesothelioma cell lines express the Angiopoietin-1/-2 and Tie-2, murine Tek-deltaFc hampered AB1 but not AE17 mesothelioma growth in vivo by enhancing tumor cell apoptosis and limiting tumor angiogenesis. Neither angiopoietins (Angs)-1 and -2 nor the inhibitor affected mesothelioma cell growth in vitro. AB1 (responding) tumors were more vascularized and displayed higher endothelial Tie-2 and lower tumor Ang-1 expression than the (non-responding) AE17 tumors. Angiopoietins-1 and -2 are expressed in tumors and pleural cavity of mesothelioma patients demonstrating the clinical relevance of our experimental observations. In conclusion, d...Continue Reading

References

Apr 1, 1995·Cancer Immunology, Immunotherapy : CII·H Bielefeldt-OhmannD R Fitzpatrick
Jun 5, 2003·Expert Opinion on Investigational Drugs·Stelios TsigkosAndreas Papapetropoulos
Jul 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nicholas J VogelzangPaolo Paoletti
Nov 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Connie JackamanDelia J Nelson
Nov 15, 2003·Laboratory Investigation; a Journal of Technical Methods and Pathology·Arup DasPaul McGuire
Feb 3, 2005·Journal of Cell Science·Marion ScharpfeneckerHellmut G Augustin
Jul 25, 2008·Nature Reviews. Cancer·Gabriele Bergers, Douglas Hanahan
Feb 27, 2009·Neoplasia : an International Journal for Oncology Research·Charalampos MoschosIoannis Kalomenidis
Feb 27, 2010·The European Respiratory Journal·C TabataT Nakano
Jul 17, 2010·The British Journal of Dermatology·C A StatonN J Brown
Jul 24, 2010·Nature Reviews. Cancer·Hanhua HuangRodney Lappe
Dec 15, 2012·Respirology : Official Journal of the Asian Pacific Society of Respirology·Androniki KollintzaIoannis Kalomenidis
Feb 15, 2013·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Birgitta I Hiddinga, Jan P van Meerbeeck
Nov 21, 2014·Particle and Fibre Toxicology·Susanne RittinghausenDirk Schaudien
Aug 1, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·P BaasUNKNOWN ESMO Guidelines Committee
Aug 8, 2015·Respirology : Official Journal of the Asian Pacific Society of Respirology·Maria Eleni VazakidouIoannis Kalomenidis
Aug 26, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael B AtkinsAlain Ravaud
Mar 5, 2016·Expert Review of Anticancer Therapy·Laurel M SchunselaarPaul Baas

❮ Previous
Next ❯

Citations

Dec 24, 2019·Frontiers in Oncology·Gerard J ChuJohn E J Rasko
Apr 10, 2021·Scientific Reports·Toshiyuki SekiAikou Okamoto
Oct 28, 2019·EBioMedicine·Nicolas AlcalaLynnette Fernandez-Cuesta

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
immunoprecipitation
ELISA

Software Mentioned

Statistical Package for the Social Sciences
ImageJ

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis