Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells

Mazzieri, Roberta, Pucci, Ferdinando, Moi, Davide, Zonari, Erika, Ranghetti, Anna, Berti, Alvise, Politi, Letterio S., Gentner, Bernhard, Brown, Jeffrey L., Naldini, Luigi and De Palma, Michele (2011) Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell, 19 4: 512-526. doi:10.1016/j.ccr.2011.02.005


Author Mazzieri, Roberta
Pucci, Ferdinando
Moi, Davide
Zonari, Erika
Ranghetti, Anna
Berti, Alvise
Politi, Letterio S.
Gentner, Bernhard
Brown, Jeffrey L.
Naldini, Luigi
De Palma, Michele
Title Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells
Journal name Cancer Cell   Check publisher's open access policy
ISSN 1535-6108
1878-3686
Publication date 2011-04-12
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.ccr.2011.02.005
Open Access Status Not Open Access
Volume 19
Issue 4
Start page 512
End page 526
Total pages 15
Place of publication Cambridge, MA United States
Publisher Cell Press
Language eng
Formatted abstract
Tumor-infiltrating myeloid cells convey proangiogenic programs that counteract the efficacy of antiangiogenic therapy. Here, we show that blocking angiopoietin-2 (ANG2), a TIE2 ligand and angiogenic factor expressed by activated endothelial cells (ECs), regresses the tumor vasculature and inhibits progression of late-stage, metastatic MMTV-PyMT mammary carcinomas and RIP1-Tag2 pancreatic insulinomas. ANG2 blockade did not inhibit recruitment of MRC1+ TIE2-expressing macrophages (TEMs) but impeded their upregulation of Tie2, association with blood vessels, and ability to restore angiogenesis in tumors. Conditional Tie2 gene knockdown in TEMs was sufficient to decrease tumor angiogenesis. Our findings support a model wherein the ANG2-TIE2 axis mediates cell-to-cell interactions between TEMs and ECs that are important for tumor angiogenesis and can be targeted to induce effective antitumor responses.
Keyword Oncology
Cell Biology
Oncology
Cell Biology
CELL BIOLOGY
ONCOLOGY
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 243128/TIE2+Monocytes
IG-2007
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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