Increased, Motility

Cell motility is the capacity of cells to translocate onto a solid substratum.

In order to move several actions such as : cell–substrate adhesion, cell–cell adhesion, cell cortex rigidity (membrane and cytoskeleton), actin polymerization-mediated protrusion and actomyosin contractility (Stuelten, Lauffenburger, Montell).

Several key factors contribute to cell motility in cancer (Friedl, Lamouille, Sahail):

• Actin Cytoskeleton Dynamics: The actin cytoskeleton plays a crucial role in cell motility. Remodeling of the actin cytoskeleton is essential for cell shape changes, protrusion formation, and cell migration. This process is tightly regulated by proteins such as actin polymerization factors, focal adhesion proteins, and myosin motors.
• Cell Adhesion and Extracellular Matrix (ECM) Interactions: Integrins and other cell adhesion molecules mediate the interaction between cancer cells and the ECM. These interactions activate signaling pathways that influence cell motility. Changes in adhesion molecules can enhance or inhibit the migratory potential of breast cancer cells.
• Epithelial-Mesenchymal Transition (EMT): EMT is a biological process in which epithelial cells acquire mesenchymal characteristics, including increased motility. EMT is associated with the invasive behavior of cancer cells, allowing them to detach from the primary tumor and migrate to distant sites.
• Chemotaxis and Gradients: Cancer cells can respond to chemical gradients, a process known as chemotaxis. Growth factors and cytokines in the tumor microenvironment can attract or repel cancer cells, influencing their direction of movement.
• Proteolytic Enzymes and Matrix Metalloproteinases (MMPs): Proteolytic enzymes, especially MMPs, are involved in degrading the ECM, facilitating cancer cell invasion. The degradation of the surrounding matrix creates space for cell movement and allows cancer cells to penetrate adjacent tissues.

In breast cancer, cell motility can favor metastasis through different steps: loss of epithelial polarity, breakdown of tissue architecture, breach of the basement membrane, intravasation, extravasation, migration into new tissues, and expansion of metastatic colonies (Stuelten). For instance, an increase in invasion of the surrounding tissues and blood vessels. Once cancer cells have invaded the local tissue, they may enter the bloodstream through a process called intravasation. Subsequently, they must migrate through the vasculature to reach distant organs, a process known as extravasation (Chambers). Once in the circulation, cells utilize chemotaxis, responding to chemokines and other signals in the microenvironment, to navigate through the bloodstream and reach specific distant organs. The ability of cancer cells to home in on specific organs depends on their motility and the interactions with the target tissue (Psaila, Labelle). Once cancer cells reach a distant organ, they need to extravasate and establish micrometastases. Motility enables cancer cells to navigate through the tissue, invade the local environment, and form secondary tumor foci (Nguyen).

Several assays can be used to measure cell motility, and the choice depends on the specific requirements and characteristics of the cells being studied. Here are some commonly used assays for measuring cell motility (Justus)

• Wound Healing Assay (Scratch Assay):

Principle: Create a controlled "wound" or scratch in a cell monolayer and monitor the closure of the gap over time.

Measurement: Quantify the rate of cell migration by measuring the reduction in the wound area.

• Transwell Migration Assay:

Principle: Cells migrate through a porous membrane from one side to the other in response to a chemoattractant.

Measurement: Count the number of cells that have migrated through the membrane or quantify fluorescence if cells are labeled.

• Boyden Chamber Assay:

Principle: Similar to the Transwell assay, cells migrate through a membrane towards a chemoattractant.

Measurement: Assess the migrated cells on the lower surface of the membrane.

• Time-Lapse Microscopy:

Principle: Track the movement of individual cells over time using live-cell imaging.

Measurement: Analyze cell trajectories, speed, and directionality.

• Collagen Invasion Assay:

Principle: Assess cell invasion through a three-dimensional collagen matrix.

Measurement: Quantify the extent of cell invasion into the matrix

• Fluorescence Recovery After Photobleaching (FRAP):

Principle: Measure the mobility of fluorescently labeled molecules or proteins within cells.

Measurement: Assess the recovery of fluorescence in a photobleached region over time.

• Single-Cell Tracking:

Principle: Monitor individual cell movements using time-lapse microscopy.

Measurement: Analyze parameters such as speed, persistence, and directionality for each tracked cell.

• Electric Cell-Substrate Impedance Sensing (ECIS):

Principle: Measure changes in electrical impedance as cells migrate and interact with a substrate.

Measurement: Quantify impedance-based parameters to assess cell motility.

• Bead-Based Motility Assay:

Principle: Attach beads to cells and track their movement using microscopy.

Measurement: Analyze the displacement of beads to determine cell motility.

Selecting the most appropriate assay depends on factors such as the nature of the cells, the desired readout, and the specific aspects of cell motility being investigated. Researchers often use a combination of these assays to gain a comprehensive understanding of cell motility in different contexts

Cell motility has been largely described in human breast cancer cell lines, mice and fish (Stuelten)

Stuelten, C., Parent, C. & Montell, D. Cell motility in cancer invasion and metastasis: insights from simple model organisms. Nat Rev Cancer 18, 296–312 (2018). https://doi.org/10.1038/nrc.2018.15

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