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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Srivastava K,Hu J,Korn C,Savant S,Teichert M,Kapel SS,Jugold M,Besemfelder E,Thomas M,Pasparakis M,Augustin HGdoi
10.1016/j.ccell.2014.11.005subject
Has Abstractpub_date
2014-12-08 00:00:00pages
880-895issue
6eissn
1535-6108issn
1878-3686pii
S1535-6108(14)00456-5journal_volume
26pub_type
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