Targeting of VEGF‐dependent transendothelial migration of cancer cells by bevacizumab

Prager, Gerald W.; Lackner, Eva; Krauth, Maria‐Theresa; Unseld, Matthias; Poettler, Marina; Laffer, Sylvia; Cerny-Reiterer, Sabine; Lamm, Wolfgang; Kornek, Gabriela; Binder, Bernd R.; Zielinski, Christoph; Valent, Peter

doi:10.1016/j.molonc.2010.01.002

Cited by 35 publications

(33 citation statements)

References 52 publications

(86 reference statements)

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“…35 In a recent study, high VEGF concentrations were shown to increase the permeability of the endothelial monolayer, which promotes cells transmigration. 28 Since MSC can differentiate into endothelial-like cells in vitro under high VEGF concentrations, 25 it is speculated that MSC may behave similarly. Indeed, CD34 + HC transmigration through the MSC monolayer was significantly up-regulated after pre-incubating the MSC layer with conditioned medium that contained a high concentration of VEGF.…”

Section: Discussionmentioning

confidence: 99%

“…28 In order to examine the effect of VEGF on the MSC monolayer we performed a HC-MSC transmigration assay. In brief, the confluent MSC monolayer was pre-incubated with conditioned medium from either the atmospheric oxygen or low oxygen co-culture with or without anti-VEGF antibodies, as described in the Design and Methods section.…”

Section: Vascular Endothelium Growth Factor-a Secretion By Mesenchymamentioning

confidence: 99%

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Oxygen tension plays a critical role in the hematopoietic microenvironment in vitro

Jing

Wobus²,

Poitz³

et al. 2011

Haematologica

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BackgroundIn the bone marrow mesenchymal stromal cells and osteoblasts form functional niches for hematopoietic stem and progenitor cells. This microenvironment can be partially mimicked using in vitro co-culture systems. In this study, we examined the oxygen tension in three distinct compartments in a co-culture system of purified CD34 + cells and mesenchymal stromal cells with regard to different spatial localizations. Design and MethodsHypoxic cells in the co-culture were visualized by pimonidazole staining. Hematopoietic cell distribution, and functional and phenotypic characteristics were analyzed by flow cytometry. The secretion of vascular endothelial growth factor and stromal-derived factor-1 by mesenchymal stromal cells in low oxygen co-cultures was determined by an enzyme-linked immunosorbent assay. The effect of co-culture medium on the hematopoietic cell migration potential was tested in a transwell assay. ResultsIn co-cultures under atmospheric oxygen tension, regions of low oxygen tension could be detected beneath the feeder layer in which a reservoir of phenotypically more primitive hematopoietic cells is located in vitro. In low oxygen co-culture, the adhesion of hematopoietic cells to the feeder layer was decreased, whereas hematopoietic cell transmigration beneath mesenchymal stromal cells was favored. Increased vascular endothelial growth factor-A secretion by mesenchymal stromal cells under low oxygen conditions, which increased the permeability of the monolayer, was responsible for this effect. Furthermore, vascular endothelial growth factor-A expression in low oxygen mesenchymal stromal cells was induced via hypoxia-inducible factor signaling. However, stromal cell-derived factor-1 secretion by mesenchymal stromal cells was down-regulated under low oxygen conditions in a hypoxia-inducible factorindependent manner. ConclusionsWe demonstrate for the first time that differences in oxygen tension cause selective modification of hematopoietic cell and mesenchymal stromal cell interactions in a co-culture system, thus confirming that oxygen tension plays a critical role in the interaction between hematopoietic cells and the niche environment.

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Section: Discussionmentioning

confidence: 99%

Section: Vascular Endothelium Growth Factor-a Secretion By Mesenchymamentioning

confidence: 99%

Oxygen tension plays a critical role in the hematopoietic microenvironment in vitro

Jing

Wobus²,

Poitz³

et al. 2011

Haematologica

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“…First, we evaluated the potential effects of cilengitide on integrin-specific cell behavior, such as cell adhesion, cell spreading and cell migration in MDA-MB-231 breast cancer cells, the same cell line used in the study mentioned above. MDA-MB-231 breast cancer cells are characterized by high integrin αVβ5 and low αVβ3 expression [35,37]. As shown in Fig.…”

Section: Cilengitide Impairs Mda-mb-231 Breast Cancer Cell Behaviormentioning

confidence: 94%

“…However, these studies did not address the biological rational for this observation. As the MDA-MB-231 breast cancer cell line used in these studies expresses αVβ3 integrins [35], any potential effect of cilengitide on osteoclasts was so far not shown. In this study, we aimed to investigate whether cilengitide reduces osteolytic lesions via inhibition of breast cancer cells or as speculated, via inhibition of osteoclasts.…”

Section: Introductionmentioning

confidence: 99%

Effects of cilengitide in osteoclast maturation and behavior

Chillà¹,

Bianconi²,

Geetha³

et al. 2015

Experimental Cell Research

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“…Cell migration was assayed in a modified boyden chamber system using transwell membranes (8 lm) (Nunc, Landenselbold, Germany) coated with gelatin, as described before [20]. Endothelial cells (2 Â 10 4 ) were added to the top chamber in the presence or absence of erlotinib, sorafenib or DMSO control.…”

Section: Angiogenesis Assaysmentioning

confidence: 99%