Identification of functional VEGF receptors on human platelets

Selheim, Frode; Holmsen, Holm; Vassbotn, Flemming S.

doi:10.1016/s0014-5793(02)02232-9

Cited by 54 publications

(45 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, platelets also contain cryptic VEGF receptors, including KDR, which become exposed on the platelet membrane upon stimulation by VEGF. 26 Although it can be argued that platelets are readily discerned by their size and the absence of a nucleus, this assumption is fundamentally flawed if platelet proteins can be transferred to other cell types. 27 After platelet activation, a myriad of platelet MPs accumulates at sites of tissue injury and leaks into the circulation.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures

Prokopi

Pula

Mayr

et al. 2009

Blood

256

182

View full text Add to dashboard Cite

IntroductionNumerous studies have demonstrated that endothelial progenitor cells (EPCs) are present among peripheral blood mononuclear cells (PBMNCs) and represent a subset of circulating bone marrow mononuclear cells (BMCs), which have the capacity to differentiate into endothelial cells in vivo. 1 New concepts of stem cell-based therapies for myocardial regeneration resulted in a rapid translation into a clinical context. [2][3][4] Yet, key questions remain unanswered. Importantly, the nomenclature and the phenotype of EPCs are subject to ongoing controversy and there are currently no specific markers that unambiguously identify these cells. 5,6 Thus, a more comprehensive approach is needed to analyze their antigenic profiles.MPs are small membrane vesicles (0.2-1.0 m) that originate from the plasma membrane and are shed from the cell surface after activation and apoptosis. 7 Importantly, MPs retain membrane antigens specific for the parent cell they originate from. Thus, MPs represent an ideal subproteome to clarify the cellular progeny of EPC cultures and mass spectrometry is the instrument of choice for this kind of research. 8 In this study, we used a proteomic approach to identify membrane proteins present on MPs in EPC cultures. Methods EPC cultureThe study was approved by the ethics review board of J. W. Goethe University and King's College London. Peripheral blood was collected from healthy adult volunteers and informed consent was obtained in accordance with the Declaration of Helsinki. EPC cultures were performed as previously described. 9,10 In brief, PBMNCs from healthy volunteers were isolated by Lymphoprep (1.077 g/mL; Axis-Shield PoCAS) density barrier centrifugation. The low-density fraction (Ͻ 1.077 g/mL) was carefully removed from the interface and washed 3 times with PBS (Dulbecco phosphate-buffered saline; Sigma-Aldrich) containing 2% FBS (fetal bovine serum, filtered and heat inactivated; Gibco, Invitrogen). Immediately after isolation, the cells were counted and 8 ϫ 10 6 cells were plated on fibronectin-coated (10 g/mL fibronectin from human plasma; SigmaAldrich) 12-well plates containing 1 mL endothelial basal medium (EBM; Cambrex Bio Science) supplemented with 20% FBS, EGM SingleQuots (10 g/mL epidermal growth factor, 3 g/mL bovine brain extract, 50 g/mL gentamicine, 50 g/mL amphotericin-B, 1 g/mL hydrocortisone; Cambrex Bio Science) and 10 ng/mL human vascular endothelial growth factor 165 (hVEGF 165; R&D Systems). Before use, the medium was passed through a 0.2-m filter. After 3 days in culture, the nonadherent An Inside Blood analysis of this article appears at the front of this issue.The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. For personal use only. on May 11, 2018. by guest www.bloodjournal.org From cells were removed and fresh EBM medium was added. T...

show abstract

Section: Discussionmentioning

confidence: 99%

Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures

Prokopi

Pula

Mayr

et al. 2009

Blood

256

182

View full text Add to dashboard Cite

show abstract

“…Both receptors are expressed on subsets of hematopoietic cells such as hematopoietic stem cells, monocytes, and platelets for VEGFR-1 (43,51) and hematopoietic stem cells, endothelial progenitors, and platelets for VEGFR-2 (10,51). This overlap in VEGF receptor expression makes it difficult to specifically study the role of each individual receptor.…”

Section: Vegfr-2 Signaling In Hematopoietic Progenitorsmentioning

confidence: 99%

Vascular Endothelial Growth Factor Receptor-2 Induces Survival of Hematopoietic Progenitor Cells

Larrivée

Lane

Pollet

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF) and its receptors play an essential role in the formation and maintenance of the hematopoietic and vascular compartments. The VEGF receptor-2 (VEGFR-2) is expressed on a population of hematopoietic cells, although its role in hematopoiesis is still unclear. In this report, we have utilized a strategy to selectively activate VEGFR-2 and study its effects in primary bone marrow cells. We found that VEGFR-2 can maintain the hematopoietic progenitor population in mouse bone marrow cultured in the absence of exogenous cytokines. Maintenance of the hematopoietic progenitor population is due to increased cell survival with minimal effect on proliferation. Progenitor survival is mainly mediated by activation of the phosphatidylinositol 3 -kinase/Akt pathway. Although VEGFR-2 also activated Erk1/2 mitogen-activated protein kinase, it did not induce cell proliferation, and blockade of this pathway only partially decreased VEGFR-2-mediated survival of hematopoietic progenitors. Thus, the role of VEGFR-2 in hematopoiesis is likely to maintain survival of hematopoietic progenitors through the activation of antiapoptotic pathways.

show abstract

“…VEGF expression is upregulated in the majority of human tumours, where it stimulates proliferation, migration and survival of endothelial cells by binding to two high-affinity tyrosine kinase receptors, VEGFR-1/Flt-1 and VEGFR-2/KDR. VEGF receptors (VEGFRs) are mainly expressed by endothelial cells, although they have also been detected in other cell types, including macrophages, monocytes (1) and platelets (2). More recently, it was shown that both VEGF and its receptors are expressed in haematological (3), pancreatic (4) and prostatic (5) tumour cells, where they may serve as autocrine stimulators of proliferation, migration and survival.…”

Section: Introductionmentioning

confidence: 99%

Expression of vascular endothelial growth factor (VEGF) and its receptors in thyroid carcinomas of follicular origin: a potential autocrine loop

Vieira¹,

Santos

Espadinha

et al. 2005

eur j endocrinol

View full text Add to dashboard Cite

Objective: The aim of this study was to clarify the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) pathways in thyroid tumourigenesis. Methods: We examined VEGF, VEGFR-1 and VEGFR-2 expression on 34 papillary thyroid carcinomas (PTCs), 18 follicular thyroid carcinomas (FTCs), eight poorly differentiated thyroid carcinomas (PDTCs) and on a thyroid tumour-derived cell line (NPA 0 87) by immunohistochemistry, reverse transcriptase PCR, immunofluorescence and Western blotting. Results: We have demonstrated that VEGF expression was significantly (P , 0.05) more prevalent in PTCs (79%) than in FTCs (50%) or PDTCs (37%). Similarly, 76% of PTCs, 83% of FTCs and 25% of PDTCs expressed VEGFR-1, whereas 68% of PTCs, 56% of FTCs and 37% of PDTCs expressed VEGFR-2. Coexpression of VEGF and its receptors was observed in 50% of PTCs, 39% of FTCs and 12% of PDTCs, raising the possibility that VEGF may signal in an autocrine loop in these neoplasias, as observed previously for other types of cancer. In agreement with the idea that autocrine VEGF signalling plays an important role in thyroid carcinogenesis, the blockade of either VEGF or its receptors with neutralizing antibodies significantly reduced cell viability and increased apoptosis levels of the VEGFR-positive thyroid tumour cell line NPA 0 87. Conclusions: Our results highlight a previously undefined VEGF autocrine action in thyroid carcinomas which could play a crucial role in tumour cell survival and could represent a useful therapeutic target for thyroid tumours.European Journal of Endocrinology 153 701-709

show abstract

Identification of functional VEGF receptors on human platelets

Cited by 54 publications

References 25 publications

Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures

Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures

Vascular Endothelial Growth Factor Receptor-2 Induces Survival of Hematopoietic Progenitor Cells

Expression of vascular endothelial growth factor (VEGF) and its receptors in thyroid carcinomas of follicular origin: a potential autocrine loop

Contact Info

Product

Resources

About