Background: BDNF, Brain-derived neurotrophic factor is a member of the neurotrophin superfamily and is a known growth factor for both central and peripheral nervous systems. While BDNF has been shown to play a role in the development of a number clinical condition including epilepsy, Alzheimer's and Parkinson's disease, it has recently been implicated in human cancers, primarily in neurological related malignancies, as well as ovarian cancer, lung cancer and skin malignancies. We have recently reported a pivotal relationship between BDNF and disease progression and clinical outcome in human breast cancer. Certain members of the neurotrophin family have also been shown to play a role in the regulation of angiogenesis. In the present study, we examined the impact of BDNF on the biological behaviour of vascular endothelia cells.

Materials and methods. Human vascular endothelial cells were used in the present study. A human BDNF expression plasmid was constructed from a cDNA library of normal tissues. Anti-BDNF transgenes were constructed based on the secondary structure of human BDNF and used to knockdown the expression of BDNF from the cells. Vascular endothelial cells with differential expression of BDNF were generated using the expression construct. Cell-matrix adhesion, cell migration and growth were determined.

Results. Human vascular endothelial cells (HECV) expressed very low levels of BDNF, traceable by PCR method. The cells were transfected with BDNF expression plasmid, which allowed establishment of BDNF over-expressing sublines, HECVBDNFexp. Expression of BDNF had a marked influence on matrix adhesion of the endothelial cells (adhesion indices for control and HECVBDNFexp cells being 3.3± 0.83 and 2.18± 0.94, respectively, p=0.01). It is interesting to note that the change of adhesion was likely to involve the focal adhesion (FAK) pathway as a FAK inhibitor, PF573228, had a profound impact on the adhesion of both control and HECVBDNFexp cells. Manipulation of BDNF in endothelial cells had a similar effect on the cellular migration, although to a lesser degree. Conclusions. Brain-derived neurotrophic factor, BDNF, has a profound impact on the biological functions of vascular endothelial cells. This may have implications in the angiogenic process seen in solid tumours.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-05-10.

2011