PDGF-BB increases endothelial migration and cord movements during angiogenesis in vitro

Abstract

To explore direct effects of platelet-derived growth factor (PDGF) on endothelial cells during angiogenesis in vitro, we have used cloned bovine aortic endothelial cells that spontaneously form cord structures. Recently we have shown that cells forming these endothelial cords express PDGF beta-receptors and that PDGF-BB can contribute to cellular proliferation and cord formation. In this study we investigated whether PDGF-induced cellular migration might also contribute to endothelial repair and angiogenesis in vitro. Ten individual endothelial cells in cords were tracked at an early stage of cord formation by video-timelapse microscopy. PDGF-BB (100 ng/ml) induced an increase in endothelial cell movement of 67 +/- 15% as compared with diluent control. Interestingly, PDGF-BB also increased movements of entire cord structures, followed at branching points, by 53 +/- 12% over diluent control. Taken together, these video-timelapse experiments suggested that the apparent movements of single endothelial cord cells might also be due to the motion of entire underlying cord structures in response to PDGF. To analyze the response of single endothelial cord cells we therefore examined whether PDGF-induced migration contributes to endothelial repair. Abrasions were applied with a razor blade to confluent monolayers of endothelial cells at an intermediate stage of cord formation. PDGF-BB concentration-dependently increased the distance to which cord-forming endothelial cells migrated into the abrasion. An increased number of elongated, i.e., probably migrating, endothelial cells was found in the abrasion in response to PDGF-BB. However, there was no effect of PDGF-BB on the total number of endothelial cells found in the abrasion. PDGF-AA affected neither the distance to which the cells migrated nor the number of elongated cells. Actin and tubulin stainings revealed that these cytoskeletal structures were not appreciably altered by PDGF-BB. Furthermore, urokinase-type plasminogen activator transcripts were not modulated in response to PDGF-BB. We conclude that in this model of angiogenesis in vitro PDGF-BB can elicit the movement of entire cord structures, possibly via u-PA-independent mechanisms. PDGF-BB also controls the migration of single cord-forming endothelial cells. Thus, PDGF-BB possibly contributes to endothelial repair and angiogenesis by direct effects on proliferation and composite movements of PDGF beta-receptor-expressing endothelial cells and cords.

WITHDRAWN: Tumor microenvironment: A review

“…PDGFs also mediate the paracrine signaling loop between endothelial cells and vSMC/pericytes during tumor angiogenic processes. PDGFs released by the tumor cells are among the potent chemoattractants and mitogens for host mesenchymal cells, it may be reasonable to speculate PDGFs roles for cancer metastasis at the preferential organ sites [41].…”

“…The absences of extracellular matrix, since other matrix components -collagen, laminin and heparin sulfate proteoglycan are concomitantly missing. These cellular characteristics are associated with cell migration and invasive potential of malignant cells [41].…”

The role of angiogenic factors in predicting clinical outcome in severe bacterial infection in Malawian children

“…VEGF is a potent regulator of vascular permeability and angiogenesis, and in endothelial cells, induces the expression of cell-adhesion molecules and the release of cytokines and chemokines [6,7]. Platelet-derived growth factor (PDGF) has angiogenic effects and stimulates endothelial cell migration [8,9]. Despite the name "platelet derived," studies suggest that the endothelium rather than platelets might be a major source of PDGF in sepsis [10].…”

Pericytes in experimental MDA-MB231 tumor angiogenesis

“…We believe that undifferentiated CAM mesenchymal cells could be transformed by PDGF-B into either myofibroblasts, PCs, or vSMCs, depending on short-range chemotactic PDGF gradients and/or interactions with ECs in the vicinity. In a 3-D angiogenesis assay, a direct role of PDGF-B even for ECs (expressing PDGF-β receptor in vitro) during migration and cord formation was demonstrated (Thommen et al 1997). On the other hand, coculture with vSMCs made ECs downregulate their PDGF-B expression (Korff et al 2001).…”