Limits...
Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis.

Vajkoczy P, Blum S, Lamparter M, Mailhammer R, Erber R, Engelhardt B, Vestweber D, Hatzopoulos AK - J. Exp. Med. (2003)

Bottom Line: Using intravital fluorescence videomicroscopy, we further defined the multistep process of embryonic endothelial progenitor cell (eEPC) homing and incorporation.Circulating eEPCs are specifically arrested in "hot spots" within the tumor microvasculature, extravasate into the interstitium, form multicellular clusters, and incorporate into functional vascular networks.Expression analysis and in vivo blocking experiments provide evidence that the initial cell arrest of eEPC homing is mediated by E- and P-selectin and P-selectin glycoprotein ligand 1.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Klinikum Mannheim, University of Heidelberg, Mannheim, Germany.

ABSTRACT
Tissue neovascularization involves recruitment of circulating endothelial progenitor cells that originate in the bone marrow. Here, we show that a class of embryonic endothelial progenitor cells (Tie-2+, c-Kit+, Sca-1+, and Flk-1-/low), which were isolated at E7.5 of mouse development at the onset of vasculogenesis, retain their ability to contribute to tumor angiogenesis in the adult. Using intravital fluorescence videomicroscopy, we further defined the multistep process of embryonic endothelial progenitor cell (eEPC) homing and incorporation. Circulating eEPCs are specifically arrested in "hot spots" within the tumor microvasculature, extravasate into the interstitium, form multicellular clusters, and incorporate into functional vascular networks. Expression analysis and in vivo blocking experiments provide evidence that the initial cell arrest of eEPC homing is mediated by E- and P-selectin and P-selectin glycoprotein ligand 1. This paper provides the first in vivo insights into the mechanisms of endothelial progenitor cell recruitment and, thus, indicates novel ways to interfere with pathological neovascularization.

Show MeSH

Related in: MedlinePlus

Circulating eEPCs interact with the tumor endo-thelium. (A) Tumor blood vessels before cell injection after contrast enhancement with FITC-conjugated dextran. Arrows indicate direction of microvascular blood flow. (B–E) Intravital microscopic sequence of two DiI-labeled eEPCs (1 and 2) interacting with the vessel wall of the identical vascular segment indicated in A. Cells adhere either permanently (1) or temporarily (2) to the endothelium. Numbers depict sequential time points in seconds (top right).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2193947&req=5

fig2: Circulating eEPCs interact with the tumor endo-thelium. (A) Tumor blood vessels before cell injection after contrast enhancement with FITC-conjugated dextran. Arrows indicate direction of microvascular blood flow. (B–E) Intravital microscopic sequence of two DiI-labeled eEPCs (1 and 2) interacting with the vessel wall of the identical vascular segment indicated in A. Cells adhere either permanently (1) or temporarily (2) to the endothelium. Numbers depict sequential time points in seconds (top right).

Mentions: Videomicroscopy revealed two mechanisms of permanent EPC arrest within tumor blood vessels. The majority of cells (87 ± 23%) actively adhered to the tumor endothelium without affecting blood flow in this vascular segment (Fig. 2, A–E) . In contrast, the remaining cells (13 ± 23%) passively plugged tumor blood vessels by size restrictions or were trapped in dead-end vascular sprouts (Fig. 3, A–C) . In contrast, cells within control blood vessels were arrested predominantly by plugging the small caliber capillaries (3–5 μm; Fig. 3 C). This indicated clearly that active, permanent adhesion of eEPCs to blood vessel endothelium was a tumor-specific phenomenon.


Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis.

Vajkoczy P, Blum S, Lamparter M, Mailhammer R, Erber R, Engelhardt B, Vestweber D, Hatzopoulos AK - J. Exp. Med. (2003)

Circulating eEPCs interact with the tumor endo-thelium. (A) Tumor blood vessels before cell injection after contrast enhancement with FITC-conjugated dextran. Arrows indicate direction of microvascular blood flow. (B–E) Intravital microscopic sequence of two DiI-labeled eEPCs (1 and 2) interacting with the vessel wall of the identical vascular segment indicated in A. Cells adhere either permanently (1) or temporarily (2) to the endothelium. Numbers depict sequential time points in seconds (top right).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193947&req=5

fig2: Circulating eEPCs interact with the tumor endo-thelium. (A) Tumor blood vessels before cell injection after contrast enhancement with FITC-conjugated dextran. Arrows indicate direction of microvascular blood flow. (B–E) Intravital microscopic sequence of two DiI-labeled eEPCs (1 and 2) interacting with the vessel wall of the identical vascular segment indicated in A. Cells adhere either permanently (1) or temporarily (2) to the endothelium. Numbers depict sequential time points in seconds (top right).
Mentions: Videomicroscopy revealed two mechanisms of permanent EPC arrest within tumor blood vessels. The majority of cells (87 ± 23%) actively adhered to the tumor endothelium without affecting blood flow in this vascular segment (Fig. 2, A–E) . In contrast, the remaining cells (13 ± 23%) passively plugged tumor blood vessels by size restrictions or were trapped in dead-end vascular sprouts (Fig. 3, A–C) . In contrast, cells within control blood vessels were arrested predominantly by plugging the small caliber capillaries (3–5 μm; Fig. 3 C). This indicated clearly that active, permanent adhesion of eEPCs to blood vessel endothelium was a tumor-specific phenomenon.

Bottom Line: Using intravital fluorescence videomicroscopy, we further defined the multistep process of embryonic endothelial progenitor cell (eEPC) homing and incorporation.Circulating eEPCs are specifically arrested in "hot spots" within the tumor microvasculature, extravasate into the interstitium, form multicellular clusters, and incorporate into functional vascular networks.Expression analysis and in vivo blocking experiments provide evidence that the initial cell arrest of eEPC homing is mediated by E- and P-selectin and P-selectin glycoprotein ligand 1.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Klinikum Mannheim, University of Heidelberg, Mannheim, Germany.

ABSTRACT
Tissue neovascularization involves recruitment of circulating endothelial progenitor cells that originate in the bone marrow. Here, we show that a class of embryonic endothelial progenitor cells (Tie-2+, c-Kit+, Sca-1+, and Flk-1-/low), which were isolated at E7.5 of mouse development at the onset of vasculogenesis, retain their ability to contribute to tumor angiogenesis in the adult. Using intravital fluorescence videomicroscopy, we further defined the multistep process of embryonic endothelial progenitor cell (eEPC) homing and incorporation. Circulating eEPCs are specifically arrested in "hot spots" within the tumor microvasculature, extravasate into the interstitium, form multicellular clusters, and incorporate into functional vascular networks. Expression analysis and in vivo blocking experiments provide evidence that the initial cell arrest of eEPC homing is mediated by E- and P-selectin and P-selectin glycoprotein ligand 1. This paper provides the first in vivo insights into the mechanisms of endothelial progenitor cell recruitment and, thus, indicates novel ways to interfere with pathological neovascularization.

Show MeSH
Related in: MedlinePlus