Blocking Angiopoietin-2 Promotes Vascular Damage and Growth Inhibition in Mouse Tumors Treated with Small Doses of Radiation

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Kallio , P , Jokinen , E , Högström , J , Das , S , Heino , S , Lähde , M , Brodkin , J , Korhonen , E A & Alitalo , K 2020 , ' Blocking Angiopoietin-2 Promotes Vascular Damage and Growth Inhibition in Mouse Tumors Treated with Small Doses of Radiation ' , Cancer Research , vol. 80 , no. 12 , pp. 2639-2650 . https://doi.org/10.1158/0008-5472.CAN-20-0497

Title: Blocking Angiopoietin-2 Promotes Vascular Damage and Growth Inhibition in Mouse Tumors Treated with Small Doses of Radiation
Author: Kallio, Pauliina; Jokinen, Elina; Högström, Jenny; Das, Suvendu; Heino, Sarika; Lähde, Marianne; Brodkin, Jefim; Korhonen, Emilia A.; Alitalo, Kari
Other contributor: University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, HUSLAB





Date: 2020-06-15
Language: eng
Number of pages: 12
Belongs to series: Cancer Research
ISSN: 0008-5472
DOI: https://doi.org/10.1158/0008-5472.CAN-20-0497
URI: http://hdl.handle.net/10138/329172
Abstract: Abnormal vasculature in tumors leads to poor tissue perfusion and cytostatic drug delivery. Although drugs inducing vascular normalization, for example, angiopoietin-2 (Ang2)-blocking antibodies, have shown promising results in preclinical tumor models, clinical studies have so far shown only little efficacy. Because Ang2 is known to play a protective role in stressed endothelial cells, we tested here whether Ang2 blocking could enhance radiation-induced tumor vascular damage. Tumor-bearing mice were treated with anti-Ang2 antibodies every 3 or 4 days starting 3 days before 3 x 2 Gy or 4 x 0.5 Gy whole-body or tumor-focused radiation. Combination treatment with anti-Ang2 and radiation improved tumor growth inhibition and extended the survival of mice with melanoma or colorectal tumors. Single-cell RNA-sequencing revealed that Ang2 blocking rescued radiation-induced decreases inT cells and cells of the monocyte/macrophage lineage. In addition, anti-Ang2 enhanced radiation-induced apoptosis in cultured endothelial cells. In vivo, combination treatment decreased tumor vasculature and increased tumor necrosis in comparison with tumors treated with monotherapies. These results suggest that a combination of Ang2-blocking antibodies with radiation increases tumor growth inhibition and extends the survival of tumor-bearing mice. Significance: These findings offer a preclinical rationale for further testing of the use of radiation in combination with Ang2-blocking antibodies to improve the overall outcome of cancer treatment.
Subject: ENDOTHELIAL-CELLS
ANGIOGENESIS
VEGF
HYPOXIA
ANG-2
GENE
RADIOTHERAPY
PROGRESSION
MECHANISMS
EXPRESSION
3111 Biomedicine
3122 Cancers
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