title: Distinct patterns of microvascular endothelial cell morphology are determined by extracellular matrix composition.
abstract: Endothelial interactions with the extracellular matrix (ECM) play important roles in angiogenesis but whether specific ECM signals can determine specific cellular morphologies is unclear. The authors compared in vitro ECM-induced morphological responses of the phenotypically distinct human placental microvascular endothelial cells (HPMECs) with large vessel endothelial cells (HUVECs). HPMECs showed distinct patterns of reorganization in response to collagen-I or collagen-IV (monolayer disruption, sprouting, migration) and Matrigel or laminin-A (intussusception, cord formation, tubulogenesis), and an intermediate response to fibrin; whereas HUVECs responded similarly to collagen-1 and Matrigel (elongation, lattice formation, vacuolation) and showed little response to fibrin. Although the extent of collagen and Matrigel responses of HPMECs were increased by serum, acidic or basic fibroblast growth factor (aFGF, bFGF), or vascular endothelial growth factor (VEGF), and varied with matrix protein concentration, the basic patterns were matrix specific, and were independent of fibronectin. The collagen responses correlated with disruption of adherens and tight junctions and the formation of filopodial protrusions. Matrigel responses were associated with up-regulated junctional localization of VE-cadherin, and tubulogenesis developed mainly through paracellular remodeling rather than intracellular vacuolation. Overall, these findings suggest that distinct ECM interactions stimulate specific morphological responses. These signals may regulate morphological behaviour in the angiogenesis cycle, switching endothelial cells between migratory and vasculogenic phenotypes.
authors.affiliation: RAFT Institute of Plastic and Reconstructive Surgery, Mount Vernon Hospital NHS Trust, London, United Kingdom. dyej@raft.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Dye
authors.forename: L
authors.initials: L
authors.lastname: Lawrence
authors.forename: C
authors.initials: C
authors.lastname: Linge
authors.forename: L
authors.initials: L
authors.lastname: Leach
authors.forename: J
authors.initials: J
authors.lastname: Firth
authors.forename: P
authors.initials: P
authors.lastname: Clark
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D024042:Collagen Type I / Q000378:metabolism / Q000494:pharmacology; D024141:Collagen Type IV / Q000378:metabolism / Q000494:pharmacology; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D008833:Microcirculation / Q000378:metabolism / Q000648:ultrastructure*; D046529:Microscopy, Electron, Transmission; D010641:Phenotype; D010920:Placenta / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D011509:Proteoglycans / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism / Q000648:ultrastructure; D014680:Veins / Q000378:metabolism / Q000648:ultrastructure*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D003094:Collagen; D024042:Collagen Type I; D024141:Collagen Type IV; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D007797:Laminin; D011509:Proteoglycans; D000099152:Cadherin 5; C059485:matrigel; C084098:laminin A