TY - JOUR
TI - Targeting Tie-2/angiopoietin axis in experimental mesothelioma confers differential responses and raises predictive implications
AU - Magkouta, S.
AU - Pappas, A.
AU - Pateras, I.S.
AU - Kollintza, A.
AU - Moschos, C.
AU - Vazakidou, M.-E.
AU - Karavana, V.
AU - Gorgoulis, V.G.
AU - Kalomenidis, I.
JO - OncoTargets and therapy
PY - 2018
VL - 9
TODO - 31
SP - 21783-21796
PB - Impact Journals, LLC
SN - null
TODO - 10.18632/oncotarget.25004
TODO - null
TODO - 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, disrupting Ang-Tie-2 signaling limits mesothelioma angiogenesis and halts tumor progression. Tumor vascularity, endothelial Tie-2 expression and tumor Ang-1 expression may predict mesothelioma response to Tek-deltaFc. © Magkouta et al.
ER -