Srivastava, Kshitij, Hu, Junhao, Korn, Claudia, Savant, Soniya ORCID: 0000-0003-2730-8526, Teichert, Martin, Kapel, Stephanie S., Jugold, Manfred, Besemfelder, Eva, Thomas, Markus, Pasparakis, Manolis ORCID: 0000-0002-9870-0966 and Augustin, Hellmut G. (2014). Postsurgical Adjuvant Tumor Therapy by Combining Anti-Angiopoietin-2 and Metronomic Chemotherapy Limits Metastatic Growth. Cancer Cell, 26 (6). S. 880 - 896. CAMBRIDGE: CELL PRESS. ISSN 1878-3686

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Abstract

Antiangiogenic tumor therapy has failed in the adjuvant setting. Here we show that inhibition of the Tie2 ligand angiopoietin-2 (Ang2) effectively blocks metastatic growth in preclinical mouse models of postsurgical adjuvant therapy. Ang2 antibody treatment combines well with low-dose metronomic chemotherapy (LDMC) in settings in which maximum-dose chemotherapy does not prove effective. Mechanistically, Ang2 blockade could be linked to quenching the inflammatory and angiogenic response of endothelial cells (ECs) in the metastatic niche. Reduced EC adhesion molecule and chemokine expression inhibits the recruitment of tumor-promoting CCR2(+)Tie2(-) metastasis-associated macrophages. Moreover, LDMC contributes to therapeutic efficacy by inhibiting the recruitment of protumorigenic bone marrow-derived myeloid cells. Collectively, these data provide a rationale for mechanism-guided adjuvant tumor therapies.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Srivastava, KshitijUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, JunhaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korn, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Savant, SoniyaUNSPECIFIEDorcid.org/0000-0003-2730-8526UNSPECIFIED
Teichert, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kapel, Stephanie S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jugold, ManfredUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Besemfelder, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Augustin, Hellmut G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-420379
DOI: 10.1016/j.ccell.2014.11.005
Journal or Publication Title: Cancer Cell
Volume: 26
Number: 6
Page Range: S. 880 - 896
Date: 2014
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1878-3686
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BEVACIZUMAB-CONTAINING THERAPY; BREAST-CANCER; MYELOID CELLS; ANTIANGIOGENIC THERAPY; COLORECTAL-CANCER; VEGF-A; ANGIOGENESIS; ANGIOPOIETIN-2; TRIAL; EXPRESSIONMultiple languages
Oncology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42037

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