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Event: 1196

Key Event Title

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

Increased, Invasion

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, Invasion
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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

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
epithelial cell 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
Androgen receptor activation leading to prostate cancer KeyEvent Brendan Ferreri-Hanberry (send email) Under development: Not open for comment. Do not cite

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
Adults 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

Cell invasion refers to the active movement of cells into and through tissues, barriers, or extracellular matrices (ECM) (Friedl). It involves a series of coordinated processes by which cells penetrate physical barriers, navigate through the extracellular environment, and potentially reach distant locations (Hynes). It is regulated by growth factors (VEGF), signaling pathways and cell-cell interactions.

Key Steps in Cell Invasion:

  • Detachment: Detachment of cells to the extracellular matrix (ECM) or neighboring cells through interactions with adhesion molecules, including integrins and cadherins.
  • Proteolysis: Degradation of ECM components by proteolytic enzymes, such as matrix metalloproteinases (MMPs), secreted by invasive cells. This process creates pathways for cell movement.
  • Motility: Dynamic changes in the cell's cytoskeleton, involving the formation of actin-rich structures like lamellipodia and filopodia, which facilitate cell movement.
  • Intravasation: Invasion of cells into blood vessels or lymphatic vessels, allowing them to enter the circulatory system and potentially spread to distant sites.
  • Extravasation: Exit of invasive cells from the bloodstream or lymphatic vessels at a secondary site, facilitating colonization and the formation of secondary tumors.
  • Adhesion: Cells form new attachments to the ECM at the leading edge, allowing for continued movement.

There are many roles for cell invasion:

  • Development and Tissue Repair: Cell invasion is crucial during embryonic development for processes such as tissue patterning and organ formation. In adults, invasion is essential for tissue repair and regeneration.
  • Embryonic development: During development, cells migrate to form different organs and tissues, shaping the intricate structure of the organism (Heisenberg).
  • Immune Response: Immune cells use invasion to migrate to sites of infection or injury, where they participate in immune responses.
  • Angiogenesis: Endothelial cells migrate to form new blood vessels, delivering oxygen and nutrients to growing tissues or healing wounds (Carmeliet, Lamalice).
  • Wound Healing: Invasive migration of cells is essential for wound healing, allowing cells to move into the wounded area and contribute to tissue repair (Grinnell).
  • Cancer Metastasis: In cancer, invasion is a hallmark of malignancy and a critical step in metastasis. Cancer cells acquire the ability to invade surrounding tissues, enter blood or lymphatic vessels, and establish secondary tumors at distant sites (Krakhmal).

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

Several assays can be used to study cell invasion (Justus):

  • Transwell Invasion Assay: Cells migrate through a porous membrane coated with ECM proteins toward a chemoattractant (Hulkower).
  • Boyden Chamber Assay: cell migration and invasion through a porous membrane in response to a gradient of chemoattractants.
  • 3D Spheroid Invasion Assay: spheroids embedded in a 3D matrix, and invasion is assessed as cells migrate out from the spheroid into the surrounding matrix (Pijuan).
  • Collagen Invasion Assay: Cells invade through a collagen matrix, simulating the extracellular environment.
  • Matrigel Invasion Assay: Cells invade through Matrigel, a basement membrane matrix rich in ECM proteins.
  • Zymography: Assess the activity of matrix metalloproteinases (MMPs), enzymes involved in ECM degradation and cell invasion.
  • Electric Cell-Substrate Impedance Sensing (ECIS): Measure changes in electrical impedance as cells invade and interact with a substrate.
  • Microfluidic Invasion Assays: Use microfluidic devices to create controlled environments for studying cell invasion (Fonseca).
  • In Vivo Invasion Assays: Intravital imaging or xenograft models to study cell invasion in vivo.

Domain of Applicability

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

Human 

Mice

References

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

Justus CR, Leffler N, Ruiz-Echevarria M, Yang LV. In vitro cell migration and invasion assays. J Vis Exp. 2014 Jun 1;(88):51046. doi: 10.3791/51046. PMID: 24962652; PMCID: PMC4186330.

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.

Pijuan J, Barceló C, Moreno DF, Maiques O, Sisó P, Marti RM, Macià A, Panosa A. In vitro Cell Migration, Invasion, and Adhesion Assays: From Cell Imaging to Data Analysis. Front Cell Dev Biol. 2019 Jun 14;7:107. doi: 10.3389/fcell.2019.00107. PMID: 31259172; PMCID: PMC6587234.

Hulkower KI, Herber RL. Cell migration and invasion assays as tools for drug discovery. Pharmaceutics. 2011 Mar 11;3(1):107-24. doi: 10.3390/pharmaceutics3010107. PMID: 24310428; PMCID: PMC3857040.

Friedl, P., & Weigelin, B. (2008). Interstitial cell migration and invasion in tumorous environments: Past, present and future. Cell adhesion & migration, 2(1), 115-125. https://pathsocjournals.onlinelibrary.wiley.com/doi/full/10.1002/path.3031

Hynes, R. O. (2009). The extracellular matrix in action. Cell, 137(5), 910-921. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185430/

Krakhmal NV, Zavyalova MV, Denisov EV, Vtorushin SV, Perelmuter VM. Cancer Invasion: Patterns and Mechanisms. Acta Naturae. 2015 Apr-Jun;7(2):17-28. PMID: 26085941; PMCID: PMC4463409.

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.

Heisenberg, C. P., & Bellairs, R. (2013). Cell migration in development and disease. Nature reviews. Molecular cell biology, 14(7), 481-494. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457291/

Grinnell, F. (2003). Fibroblast biology: From contraction to proliferation. Journal of cell physiology, 197(1), 301-303. https://pubmed.ncbi.nlm.nih.gov/8106541/

Carmeliet, P., & Jain, R. K. (2011). Angiogenesis in disease and the angiogenic switch. Nature medicine, 17(7), 755-763