Endothelial-pericyte interactions in angiogenesis

Gerhardt, Holger; Betsholtz, Christer

doi:10.1007/s00441-003-0745-x

Cited by 953 publications

(806 citation statements)

References 77 publications

Supporting

Mentioning

767

Contrasting

Unclassified

Order By: Relevance

“…The astrocyte network strongly affects vascular patterning (Fruttiger et al, 1996). Endothelial cells at the leading edge of the vascular plexus possess long filopodia that closely follow the underlying astrocyte scaffold (Dorrell et al, 2002;Gerhardt and Betsholtz, 2003). Interaction of astrocytes with capillary-like structures of brain microvessel endothelium plays an important role in regulating angiogenesis and BBB leakage (Jiang et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

Zacharek¹,

Chen²,

Cui³

et al. 2007

J Cereb Blood Flow Metab

257

201

View full text Add to dashboard Cite

Bone marrow stromal cells (MSCs) increase vascular endothelial growth factor (VEGF) expression and promote angiogenesis after stroke. Angiopoietin-1 (Ang1) and its receptor Tie2 mediate vascular integrity and angiogenesis as does VEGF and its receptors. In this study, we tested whether MSC treatment of stroke increases Ang1/Tie2 expression, and whether Ang1/Tie2 with VEGF/ vascular endothelial growth factor receptor 2 (VEGFR2) (Flk1), in combination, induced by MSCs enhances angiogenesis and vascular integrity. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAo) and treated with or without MSCs. Marrow stromal cell treatment significantly decreased blood-brain barrier (BBB) leakage and increased Ang1,

show abstract

Section: Discussionmentioning

confidence: 99%

Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

Zacharek¹,

Chen²,

Cui³

et al. 2007

J Cereb Blood Flow Metab

257

201

View full text Add to dashboard Cite

show abstract

“…Endothelial cells recruit PDGF-expressing pericytes that function to stabilize the outer lining of newly developing vasculature for angiogenesis (Gerhardt and Betsholtz, 2003). Indeed, the expression of PDGF-B is observed mainly at sites where active angiogenesis occurs (Hellstrom et al, 1999;2001).…”

Section: Pericyte/vsm-endothelial Cell Interactions In the Tumor Micrmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

693

327

View full text Add to dashboard Cite

High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells, microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. V

show abstract

“…PCs are recruited by PDGF-B expressing ECs to stabilize and mature new vessels. [1][2][3] Either PDGF-B or PDGFR-Beta knockout mice suffer from vascular leakage, hemorrhage and edema due to a deficit in PC blood vessel coverage. [4][5][6] In neoplastic angiogenesis, PCs seem to be reduced in number and to have abnormalities in their contact with ECs.…”

mentioning

confidence: 99%

Circulating perivascular progenitors: A target of PDGFR inhibition

Mancuso

Martín‐Padura

Calleri

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

Cancer blood vessels consist of two interacting types of cells: inner lining endothelial cells (ECs) and surrounding perivascular cells (pericytes, vascular smooth muscle cells or mural cells). PDGFRbeta(CD140b)+ progenitor perivascular cells (PPC) can differentiate into pericytes and regulate vessel stability and vascular survival in tumors. Similarly to what we have done with circulating ECs and progenitors, we developed a flow cytometry procedure for the enumeration of circulating PPCs and the study of their viability in murine models of cancer and in cancer patients. DNA+CD45−CD31−CD140b+ cells were enumerated by six‐colour flow cytometry, their morphology was studied by electron microscopy, PPC specificity confirmed by reverse trascription‐PCR (RT‐PCR) expression of CD140b mRNA, and viability assessed by Syto16 and 7AAD. In preclinical marrow transplantation studies, 9 ± 4% of circulating PPCs were derived from the marrow donor. PPCs were increased in cancer‐bearing mice and in patients affected by some types of cancer. At variance with the kinetic of circulating endothelial progenitors, high‐dose cyclophosphamide reduced the number of viable PPCs. The administration of sunitinib, a drug known to inhibit PDGFR, was associated in murine models and in cancer patients with an increase of apoptotic/necrotic circulating PPC, suggesting a direct targeting of these cells. PPC enumeration might be studied as a tool for the definition of the optimal biologic dose of anti‐PDGFR drugs and investigated clinically as a possible predictive/prognostic tool in patients receiving anti‐PDGFR drugs.

show abstract

Endothelial-pericyte interactions in angiogenesis

Cited by 953 publications

References 77 publications

Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

The brain tumor microenvironment

Circulating perivascular progenitors: A target of PDGFR inhibition

Contact Info

Product

Resources

About