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 |
Contributor organization: | CAN-PRO - Translational Cancer Medicine Program University of Helsinki Digital Precision Cancer Medicine (iCAN) Research Programs Unit HUSLAB Kari Alitalo / Principal Investigator |
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 |
Peer reviewed: | Yes |
Rights: | unspecified |
Usage restriction: | openAccess |
Self-archived version: | acceptedVersion |
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