We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Axl as a potential therapeutic target in cancer: role of Axl in tumor growth, metastasis and angiogenesis.
- Authors
Li, Y.; Ye, X.; Tan, C.; Hongo, J.-A.; Zha, J.; Liu, J.; Kallop, D.; Ludlam, M. J. C.; Pei, L.
- Abstract
Dysregulation of Axl and its ligand growth arrest-specific 6 is implicated in the pathogenesis of several human cancers. In this study, we have used RNAi and monoclonal antibodies to assess further the oncogenic potential of Axl. Here we show that Axl knockdown reduces growth of lung and breast cancer xenograft tumors. Inhibition of Axl expression attenuates breast cancer cell migration and inhibits metastasis to the lung in an orthotopic model, providing the first in vivo evidence that links Axl directly to cancer metastasis. Axl knockdown in endothelial cells impaired tube formation and this effect was additive with anti-vascular endothelial growth factor (VEGF). Further analysis demonstrated that Axl regulates endothelial cell functions by modulation of signaling through angiopoietin/Tie2 and Dickkopf (DKK3) pathways. We have developed and characterized Axl monoclonal antibodies that attenuate non-small cell lung carcinoma xenograft growth by downregulation of receptor expression, reducing tumor cell proliferation and inducing apoptosis. Our data demonstrate that Axl plays multiple roles in tumorigenesis and that therapeutic antibodies against Axl may block Axl functions not only in malignant tumor cells but also in the tumor stroma. The additive effect of Axl inhibition with anti-VEGF suggests that blocking Axl function could be an effective approach for enhancing antiangiogenic therapy.
- Subjects
CELL migration; METASTASIS; GROWTH factors; ONCOGENIC viruses; BREAST cancer; LUNG cancer
- Publication
Oncogene, 2009, Vol 28, Issue 39, p3442
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2009.212