The purpose of these experiments was to evaluate the expression of endothelial markers, such as Tie2 and VEGFR2 in endothelial cells derived from blood mononuclear endothelial progenitor cells. Bovine mononuclear cells were isolated using separation by centrifugation and were grown in endothelial specific media supplemented with growth factors. Isolation of the whole cell population of mononuclear cells (MNC) from bovine peripheral blood gave rise to progenitor-like cells (CD45(-)) that, although morphologically similar, have different phenotypes revealed by expression of endothelial specific markers Tie2 and VEGFR2.
View Article and Find Full Text PDFReceptors for the angiogenic factor VEGF are expressed by tumor cancer cells including melanoma, although their functionality remains unclear. Paired human melanoma cell lines WM115 and WM239 were used to investigate differences in expression and functionality of VEGF and VEGFR2 in vitro and in vivo with the anti-VEGF antibody bevacizumab. Both WM115 and WM239 cells expressed VEGF and VEGFR2, the levels of which were modulated by hypoxia.
View Article and Find Full Text PDFAntiangiogenic therapy is theoretically a promising anticancer approach but does not always produce significant tumor control. Combinations of antiangiogenic therapies are therefore being investigated as strategies to enhance clinical benefit. Common targets for angiogenic blockade include endothelial specific receptors, such as Tie2/Tek, which signal blood vessel stabilization via recruitment and maturation of pericytes.
View Article and Find Full Text PDFBackground: Targeting tumor vasculature is a strategy with great promise in the treatment of many cancers. However, anti-angiogenic reagents that target VEGF/VEGFR2 signaling have met with variable results clinically. Among the possible reasons for this may be heterogeneous expression of the target protein.
View Article and Find Full Text PDFWe examined the effect of hypoxia on apoptosis of human colorectal cancer (CRC) cells in vitro and in vivo. All cell lines tested were susceptible to hypoxia-induced apoptosis. DCA treatment caused significant apoptosis under normoxia in SW480 and Caco-2 cells, but these cells displayed decreased apoptosis when treated with DCA combined with hypoxia, possibly through HIF-1alpha dependent pathways.
View Article and Find Full Text PDFDysregulation or mislocalization of cell adhesion molecules and their regulators, such as E-cadherin, beta-catenin, and alpha-catenin, usually correlates with loss of polarity, dedifferentiation, invasive tumor growth, and metastasis. A subpopulation of alpha-catenin-negative cells within the DLD-1 colorectal carcinoma cell line causes it to display a heterogeneous morphological makeup, thus providing an excellent model system in which to investigate the role of alpha-catenin in tumorigenesis. We re-established expression of alpha-catenin protein in an alpha-catenin-deficient subpopulation of the DLD-1 cell line and used it to demonstrate that loss of alpha-catenin resulted in increased in vitro tumorigenic characteristics (increased soft agarose colony formation, clonogenic survival after suspension, and survival in suspension).
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