The soluble form of the cancer-associated L1 cell adhesion molecule is a pro-angiogenic factor |
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| Authors: | Alexandra Friedli Eliane Fischer Ilse Novak-Hofer Susan Cohrs Kurt Ballmer-Hofer P. August Schubiger Roger Schibli Jürgen Grünberg |
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| Affiliation: | 1. Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, Villigen, Switzerland;2. Paul Scherrer Institute, Laboratory of Biomolecular Research, Molecular Cell Biology, Villigen, Switzerland;3. PET-Animal Imaging Center, Federal Institute of Technology, Zurich, Switzerland;1. Department of Obstetrics and Gynecology, Buddhist Tzu-Chi General Hospital, Taipei Branch, Taipei, Taiwan;2. Department of Obstetrics and Gynecology, National Taiwan University Hospital, School of Medicine, National Taiwan University, Taipei, Taiwan;1. Institute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;2. SRC Bioclinicum, Moscow, Russia;3. Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia;4. P.A. Hertsen Moscow Research Oncology Institute, Moscow, Russia |
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| Abstract: | A soluble form of the L1 cell adhesion molecule (sL1) is released from various tumor cells and can be found in serum and ascites fluid of uterine and ovarian carcinoma patients. sL1 is a ligand for several Arg-Gly-Asp (RGD)-binding integrins and can be deposited in the extracellular matrix. In this study we describe a novel function of this physiologically relevant form of L1 as a pro-angiogenic factor. We demonstrated that the anti-L1 monoclonal antibody (mAb) chCE7 binds near or to the sixth Ig-like domain of human L1 which contains a single RGD sequence. mAb chCE7 inhibited the RGD-dependent adhesion of ovarian carcinoma cells to sL1 and reversed the sL1-induced proliferation, matrigel invasion and tube formation of bovine aortic endothelial (BAE) cells. A combination of sL1 with vascular endothelial growth factor-A (VEGF-A165), which is an important angiogenic inducer in tumors, strongly potentiated VEGF receptor-2 tyrosine phosphorylation in BAE cells. Chick chorioallantoic membrane (CAM) assays revealed the pro-angiogenic potency of sL1 in vivo which could be abolished by chCE7. These results indicate an important role of released L1 in tumor angiogenesis and represent a novel function of antibody chCE7 in tumor therapy. |
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