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Event: 1190

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased, Migration (Endothelial Cells)

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Increased, Migration (Endothelial Cells)
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
endothelial cell

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
endothelial cell migration increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
ER activation to breast cancer KeyEvent Brendan Ferreri-Hanberry (send email) Open for adoption
AhR activation to metastatic breast cancer KeyEvent Evgeniia Kazymova (send email) Under Development: Contributions and Comments Welcome Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Adult High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Mixed High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Endothelial cell migration refers to the movement of endothelial cells, which are the cells lining the inner surface of blood vessels, across tissues. This dynamic process is essential for various physiological functions, including vascular development, tissue repair, and angiogenesis (Michaelis, Fonseca)..

During migration, endothelial cells undergo a series of coordinated steps, including sensing chemotactic signals, altering their cytoskeleton to form protrusions (Extension of finger-like projections (filopodia) at the leading edge of the cell to sense the environment), adhering to the extracellular matrix through molecules such as integrins,contraction (pulling the cell forward using actin) and finally detachment for movement (Michaelis, Fonseca). These movements are crucial for the remodeling and maintenance of blood vessels. This is regulated by chemical signs (VEGG, integrins) and physical cues (Michaelis, Fonseca, Norton).

The role of endothelial cell migration is in (Michaelis, Fonseca).:

  • Angiogenesis: One of the primary roles of endothelial cell migration is in angiogenesis, the formation of new blood vessels. In response to signals from growth factors like vascular endothelial growth factor (VEGF), endothelial cells migrate towards the site of angiogenesis, contributing to the expansion of the vascular network (Michaelis, Lamalis).
  • Tissue Repair: Endothelial cell migration is crucial for repairing damaged blood vessels. In response to injury or inflammation, endothelial cells migrate to the site of damage, facilitating the restoration of vascular integrity (Michaelis).
  • Vascular Development: During embryonic development, endothelial cell migration is essential for the formation and remodeling of blood vessels (Scarpa). This process helps establish the intricate vascular network required for organ development.
  • Immune Response: Endothelial cells play a role in immune responses by facilitating the migration of immune cells across blood vessel walls to sites of infection or injury (Sturtzel).
  • Lymphangiogenesis: Endothelial cell migration is involved in lymphangiogenesis, the formation of new lymphatic vessels. This process is crucial for fluid drainage, immune surveillance, and can also play a role in cancer metastasis (Pengchung).
  • Wound Healing:Endothelial cells contribute to wound healing by migrating to the site of injury and participating in the formation of new blood vessels, a process known as neovascularization (Lamalis, Amersfoort).
  • Cancer Metastasis: In cancer, endothelial cell migration is hijacked by tumors to support their growth and metastasis. Tumor cells release angiogenic factors, inducing the migration of endothelial cells to form new blood vessels that supply nutrients to the growing tumor (Lamalis).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Assays used to study endothelial cell migration (Guo):  

  • Boyden chamber: evaluates the ability of cells to migrate through a porous membrane towards a chemoattractant (substance that attracts cells) placed in the lower chamber.
  • Scratch wound assay: collective movement of endothelial cells to close a "wound" created by scratching a confluent monolayer of cells.
  • Microfluidic assay: microfluidic channels to create controlled environments that mimic the physiological flow conditions experienced by endothelial cells in vivo (Shih)
  • Tube formation: assays evaluate the ability of endothelial cells to form tube-like structures, mimicking the process of blood vessel formation (angiogenesis) (Guo)
  • Collagen Invasion Assay: Assess the invasive capacity of endothelial cells through a three-dimensional collagen matrix
  • Time-lapse microscopy: using live-cell imaging
  • 3D spheroid migration
  • In vivo: vessel density in fat pads

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Human, breast cancer cell lines

Mice

References

List of the literature that was cited for this KE description. More help

Mierke CT. Role of the endothelium during tumor cell metastasis: is the endothelium a barrier or a promoter for cell invasion and metastasis? J Biophys. 2008;2008:183516. doi: 10.1155/2008/183516. Epub 2009 Mar 5. PMID: 20107573; PMCID: PMC2809021.

Michaelis UR. Mechanisms of endothelial cell migration. Cell Mol Life Sci. 2014 Nov;71(21):4131-48. doi: 10.1007/s00018-014-1678-0. Epub 2014 Jul 20. PMID: 25038776.

Guo S, Lok J, Liu Y, Hayakawa K, Leung W, Xing C, Ji X, Lo EH. Assays to examine endothelial cell migration, tube formation, and gene expression profiles. Methods Mol Biol. 2014;1135:393-402. doi: 10.1007/978-1-4939-0320-7_32. PMID: 24510881; PMCID: PMC4035906.

Shih, HC., Lee, TA., Wu, HM. et al. Microfluidic Collective Cell Migration Assay for Study of Endothelial Cell Proliferation and Migration under Combinations of Oxygen Gradients, Tensions, and Drug Treatments. Sci Rep 9, 8234 (2019). https://doi.org/10.1038/s41598-019-44594-5

Fonseca CG, Barbacena P, Franco CA. Endothelial cells on the move: dynamics in vascular morphogenesis and disease. Vasc Biol. 2020 Jul 2;2(1):H29-H43. doi: 10.1530/VB-20-0007. PMID: 32935077; PMCID: PMC7487603.

Yu P, Wu G, Lee HW, Simons M. Endothelial Metabolic Control of Lymphangiogenesis. Bioessays. 2018 Jun;40(6):e1700245. doi: 10.1002/bies.201700245. Epub 2018 May 11. PMID: 29750374; PMCID: PMC6237195.

Amersfoort, J., Eelen, G. & Carmeliet, P. Immunomodulation by endothelial cells — partnering up with the immune system?. Nat Rev Immunol 22, 576–588 (2022). https://doi.org/10.1038/s41577-022-00694-4

Sturtzel C. Endothelial Cells. Adv Exp Med Biol. 2017;1003:71-91. doi: 10.1007/978-3-319-57613-8_4. PMID: 28667554.

Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res. 2007 Mar 30;100(6):782-94. doi: 10.1161/01.RES.0000259593.07661.1e. PMID: 17395884.

Scarpa E, Mayor R. Collective cell migration in development. J Cell Biol. 2016 Jan 18;212(2):143-55. doi: 10.1083/jcb.201508047. PMID: 26783298; PMCID: PMC4738384.

Michaelis UR. Mechanisms of endothelial cell migration. Cell Mol Life Sci. 2014 Nov;71(21):4131-48. doi: 10.1007/s00018-014-1678-0. Epub 2014 Jul 20. PMID: 25038776.

Norton KA, Popel AS. Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis. Sci Rep. 2016 Nov 14;6:36992. doi: 10.1038/srep36992. PMID: 27841344; PMCID: PMC5107954.