References
PMID:19401151
The soluble form of the cancer-associated L1 cell adhesion molecule is a pro-angiogenic factor.
Soluble L1CAM was able to stimulate growth and invasion of bovine aortic endothelial cells to a similar extent as the VEGF-A (isoform 165 amino acids)
Stimulation with soluble L1CAM led to tube formation of bovine aortic endothelial cells in vitro and increased angiogenesis in vivo.
The pro- angiogenic effect of soluble L1CAM could be abolished by treatment with the L1CAM specific antibody chCE7.
PMID:18931829
PDAC Endothelial cells are characterized by elevated L1CAM expression compared to HUVEC cells where L1CAM expression can be induced by TNFa???IFNg???or TGFB1
Antibody-mediated blockade of L1CAM abolished tube formation and tumor endothelial cell transmigration.
Integrins, especially???v???3, play a role in the activation ofVEGFR-
2, a key player in angiogenesis. Because both sL1 and VEGF are present in ascites fluid of ovarian carcinoma patients (Fogel et al., 2003a;Zebrowskiet al.,1999),weanalyzedtheactivation ofVEGFR-
2 in BAE cells in the presence of sL1 and VEGF-A165 (Fig. 6). The three-fold higher stimulation of VEGFR-2 with the combination of bothcomponents incomparison tothe single treatmentwithVEGF-
A165 could be explained by the activation of ???v???3 integrin through the RGD sequence in the L1 molecule. ???v???3 integrin is involved in the full activation of VEGFR-2 triggered by VEGF-A165 (Soldi et al., 1999). These findings are consistent with results published by Hall and co-workers (2004); Hall and Hubbell (2004). They showed that ligation of mouse L1Ig6 to ???v???3 integrin stimulates VEGFR-2 and induces angiogenesis in vivo
Overall, these data point to a role of L1CAM as a pro-angiogenic factor and the potential of an anti-L1CAM antibody therapy in interfering with tumor angiogenesis (see below).