• Migrating through small spaces makes can

    From ScienceDaily@1:317/3 to All on Tuesday, March 08, 2022 21:30:40
    Migrating through small spaces makes cancer cells more aggressive

    Date:
    March 8, 2022
    Source:
    eLife
    Summary:
    Squeezing through tight spaces makes cancer cells more aggressive
    and helps them evade cell death, shows a new study.



    FULL STORY ========================================================================== Squeezing through tight spaces makes cancer cells more aggressive and
    helps them evade cell death, shows a study published today in eLife.


    ==========================================================================
    The findings reveal how mechanical stress makes cancer cells more
    likely to spread, or metastasise. While metastasis is the cause of
    most cancer deaths, there are currently no available cures. However,
    the new results may help scientists develop novel approaches to treat
    or prevent metastasis.

    It can be a tight squeeze for cancer cells to escape their tumour or
    enter tiny blood vessels, called capillaries, to spread through the
    body. The cells must collapse and change their shape to do this, in a
    process called confined migration. As they spread, the cells must also
    avoid detection and destruction by the immune system.

    "Mechanical stress can cause cancer cell mutations, as well as an
    uncontrolled increase in cell numbers and greater tissue invasion,"
    explains first author Deborah Fanfone, Postdoctoral Fellow at the
    Cancer Research Center of Lyon, France. "We wanted to know if the
    mechanical stress of confined migration makes cancer cells more likely to metastasise, and how this happens." To answer these questions, Fanfone
    and colleagues forced human breast cancer cells through a membrane with
    tiny, three-micrometre-sized holes to simulate a confined migration environment. After just one passage through the membrane, they found
    that the cells became more mobile and resistant to anoikis -- a form of programmed cell death that occurs when cells become detached from the surrounding network of proteins and other molecules that support them
    (the extracellular matrix). The cells were also able to escape destruction
    by immune natural killer cells.

    Further experiments showed that increased expression of
    inhibitory-of-apoptosis proteins (IAPs) increased the resistance of cancer cells to anoikis. Treating the cancer cells with a new type of cancer
    drug called a SMAC mimetic, which degrades IAPs, removed this protection.

    The team then studied how breast cancer cells that had undergone confined migration behave when administered to immune-suppressed mice. They found
    these mice developed more lung metastases than mice that were administered
    with breast cancer cells that had not been exposed to confined migration.

    "By mimicking confined migration, we've been able to explore its
    multifaceted effects on cancer aggressiveness," says senior author Gabriel Ichim, who leads the Cancer Cell Death team at the Cancer Research Center
    of Lyon. "We've shown how the process boosts survival in cancer cells
    and makes them more prone to forming deadly metastases." The authors add
    that these results may lead to additional studies of potential metastasis treatments, such as therapies that soften tumours to reduce mechanical
    stress on cancer cells, or that block IAPs. These include SMAC mimetics,
    which are currently being tested in clinical trials as a possible new
    treatment approach.


    ========================================================================== Story Source: Materials provided by eLife. Note: Content may be edited
    for style and length.


    ========================================================================== Journal Reference:
    1. Deborah Fanfone, Zhichong Wu, Jade Mammi, Kevin Berthenet,
    David Neves,
    Kathrin Weber, Andrea Halaburkova, Franc,ois Virard, Fe'lix
    Bunel, Catherine Jamard, Hector Hernandez-Vargas, Stephen WG
    Tait, Ana Hennino, Gabriel Ichim. Confined migration promotes
    cancer metastasis through resistance to anoikis and increased
    invasiveness. eLife, 2022; 11 DOI: 10.7554/eLife.73150 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220308115642.htm

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