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Effects of adrenomedullin on endothelial cells in the multistep process of angiogenesis: Involvement of CRLR/RAMP2 and CRLR/RAMP3 receptors
International journal of cancer, 2004-03, Vol.108 (6), p.797-804
Fernandez‐Sauze, Samantha
Delfino, Christine
Mabrouk, Kamel
Dussert, Christophe
Chinot, Olivier
Martin, Pierre‐Marie
Grisoli, Francois
Ouafik, L'Houcine
Boudouresque, Françoise
2004
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Fernandez‐Sauze, Samantha
Delfino, Christine
Mabrouk, Kamel
Dussert, Christophe
Chinot, Olivier
Martin, Pierre‐Marie
Grisoli, Francois
Ouafik, L'Houcine
Boudouresque, Françoise
Titel
Effects of adrenomedullin on endothelial cells in the multistep process of angiogenesis: Involvement of CRLR/RAMP2 and CRLR/RAMP3 receptors
Ist Teil von
International journal of cancer, 2004-03, Vol.108 (6), p.797-804
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2004
Quelle
MEDLINE
Beschreibungen/Notizen
Recently, we demonstrated that U87 glioblastoma xenograft tumors treated with anti‐adrenomedullin (AM) antibody were less vascularized than control tumors, suggesting that AM might be involved in neovascularization and/or vessel stabilization. Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, is a multistep process that involves migration and proliferation of endothelial cells, remodeling of the extracellular matrix and functional maturation of the newly assembled vessels. In our study, we analyzed the role of AM on human umbilical vein endothelial cell (HUVEC) phenotype related to different stages of angiogenesis. Here we report evidence that AM promoted HUVEC migration and invasion in a dose‐dependent manner. The action of AM is specific and is mediated by the calcitonin receptor‐like receptor/receptor activity‐modifying protein‐2 and ‐3 (CRLR/RAMP2; CRLR/RAMP3) receptors. Furthermore, AM was able to induce HUVEC differentiation into cord‐like structures on Matrigel. Suboptimal concentrations of vascular endothelial growth factor (VEGF) and AM acted synergistically to induce angiogenic‐related effects on endothelial cells in vitro. Blocking antibodies to VEGF did not significantly inhibit AM‐induced capillary tube formation by human endothelial cells, indicating that AM does not function indirectly through upregulation of VEGF. These findings suggest that the proangiogenic action of AM on cultured endothelial cells via CRLR/RAMP2 and CRLR/RAMP3 receptors may translate in vivo into enhanced neovascularization and therefore identify AM and its receptors acting as potential new targets for antiangiogenic therapies. © 2003 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0020-7136
eISSN: 1097-0215
DOI: 10.1002/ijc.11663
Titel-ID: cdi_hal_primary_oai_HAL_hal_01823632v1
Format
–
Schlagworte
Adrenomedullin
,
angiogenesis
,
Angiogenesis Inhibitors - pharmacology
,
Biological and medical sciences
,
Blood vessels and receptors
,
Blotting, Western
,
Cancer
,
Cell Differentiation
,
Cell Division
,
Cell Line, Tumor
,
Cell Movement
,
Cells, Cultured
,
Collagen - pharmacology
,
CRLR
,
Dose-Response Relationship, Drug
,
Drug Combinations
,
endothelial cells
,
Endothelial Cells - cytology
,
Endothelial Cells - metabolism
,
Endothelium, Vascular - cytology
,
Enzyme-Linked Immunosorbent Assay
,
Extracellular Matrix - physiology
,
Fundamental and applied biological sciences. Psychology
,
Humans
,
Intracellular Signaling Peptides and Proteins
,
Laminin - pharmacology
,
Life Sciences
,
Membrane Proteins - genetics
,
Membrane Proteins - physiology
,
Neoplasm Invasiveness
,
Neoplasm Metastasis
,
Neoplasm Transplantation
,
Neovascularization, Pathologic
,
Peptides - physiology
,
Phenotype
,
Proteoglycans - pharmacology
,
RAMP2/RAMP3
,
Receptor Activity-Modifying Protein 2
,
Receptor Activity-Modifying Protein 3
,
Receptor Activity-Modifying Proteins
,
Reverse Transcriptase Polymerase Chain Reaction
,
RNA, Messenger - metabolism
,
Umbilical Veins - cytology
,
Vascular Endothelial Growth Factor A - metabolism
,
Vertebrates: cardiovascular system
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