Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2009-10-2
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3442-55
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19633687-Animals, pubmed-meshheading:19633687-Breast Neoplasms, pubmed-meshheading:19633687-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:19633687-Cell Line, Tumor, pubmed-meshheading:19633687-Cell Movement, pubmed-meshheading:19633687-Gene Knockdown Techniques, pubmed-meshheading:19633687-Humans, pubmed-meshheading:19633687-Mice, pubmed-meshheading:19633687-Neoplasm Metastasis, pubmed-meshheading:19633687-Neoplasm Transplantation, pubmed-meshheading:19633687-Neovascularization, Pathologic, pubmed-meshheading:19633687-Oncogene Proteins, pubmed-meshheading:19633687-Proto-Oncogene Proteins, pubmed-meshheading:19633687-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:19633687-Signal Transduction, pubmed-meshheading:19633687-Transplantation, Heterologous, pubmed-meshheading:19633687-Vascular Endothelial Growth Factor A
pubmed:year
2009
pubmed:articleTitle
Axl as a potential therapeutic target in cancer: role of Axl in tumor growth, metastasis and angiogenesis.
pubmed:affiliation
Department of Molecular Oncology, Genentech Inc., South San Francisco, CA 94080, USA.
pubmed:publicationType
Journal Article