Burst of rapid cell motion in 3D tumor model
Researchers discover phenomenon to help explain cancer metastasis
Date:
March 16, 2022
Source:
University of Go"ttingen
Summary:
Biological processes such as wound healing and cancer cell invasion
rely on the collective and coordinated motion of living cells. A
little understood aspect that influences these processes is the
pressure differences within and between different parts of the
body. Researchers designed model tumor systems using cervical
cancer cells in collagen matrices to investigate whether pressure
differences can push cancer cells into their surroundings. Upon
embedding the model tumors into a soft matrix, an increased
pressure led to a sudden burst of rapid and coordinated cellular
motion that sprayed outwards from the tumor.
FULL STORY ========================================================================== Biological processes such as wound healing and cancer cell invasion
rely on the collective and coordinated motion of living cells. A little understood aspect that influences these processes is the pressure
differences within and between different parts of the body. Researchers
from Go"ttingen University and Mu"nster University designed model
tumour systems using cervical cancer cells in collagen matrices to
investigate whether pressure differences can push cancer cells into
their surroundings. Upon embedding the model tumours into a soft matrix,
an increased pressure led to a sudden burst of rapid and coordinated
cellular motion that sprayed outwards from the tumour. Their results
were published in Advanced Science.
==========================================================================
The researchers designed their model system using clumps of cervical
cancer cells in simple 3D tissues that they could control, enabling
them to systematically study the behaviour of the cells in different
pressures and environments. Usually, individual cells exert forces on
their environment in order to move, and collective motion is coordinated
by cell-to-cell forces because they stick and clump together. However,
this new model allowed the researchers to measure other mechanisms
that encourage cellular movement such as pressure differences between
different regions within the body.
Using imaging techniques that allowed the scientists to follow the tumour deformation even at the level of a single cell, the researchers discovered
that increased pressure in a soft matrix drove coordinated cellular motion independent of cell-to-cell stickiness by triggering cell swelling. Eight
hours after the 3D clumps of cervical cancer cells were embedded in soft collagen matrices, they burst out in a sudden rapid stream of cancer
cells. This fluid- like pushing mechanism exhibits high cell velocities
and a sudden super- spreading motion like water spraying from a hose when
you press your thumb over the top. In fact, the rapid burst seemed to kill about 80% of the cells but surprisingly the remaining cells succeeded
in embedding in the same environment over the following four days, and multiplied. "This signified that after the initial burst, the remaining
live cells could still divide substantially and migrate. Importantly,
when this happens in a person's body, this can prove to be extremely
dangerous, often beating current cancer treatments," explains Professor
Timo Betz, Biophysics Institute, University of Go"ttingen.
Tumour models embedded in a stiffer collagen did not behave in the
same way. In fact, even after seven days, there was a complete absence
of bursts, showing that the pressure difference in the tissue was the
important part of the effect. The only way that researchers could trigger
the "cell burst" in stiffer collagen was by introducing weak spots in
specific regions.
In this newly observed phenomenon, cell swelling in groups increased the intrinsic pressure that pushed the cancer cells out into less resistant
regions of the matrix. "Such pressure-driven effects may provide primary tumours in the body an exceptional advantage: it enables them to breach
the first membrane barrier and gives them the opportunity to spread
to other parts of the body, or metastasize," says Betz. He adds: "This
provides new evidence that pressure- driven effects should be considered
to help us better understand the mechanical forces involved in cell and
tissue movement as well as cancer cell invasion.
Understanding this cellular mass movement is fundamental for describing
and treating cancer and similar illnesses."
========================================================================== Story Source: Materials provided by University_of_Go"ttingen. Note:
Content may be edited for style and length.
========================================================================== Journal Reference:
1. Swetha Raghuraman, Ann‐Sophie Schubert, Stephan Bro"ker,
Alejandro
Jurado, Annika Mu"ller, Matthias Brandt, Bart E. Vos, Arne
D. Hofemeier, Fatemeh Abbasi, Martin Stehling, Raphael Wittkowski,
Johanna Ivaska, Timo Betz. Pressure Drives Rapid Burst‐Like
Coordinated Cellular Motion from 3D Cancer Aggregates. Advanced
Science, 2022; 9 (6): 2104808 DOI: 10.1002/advs.202104808 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220316132648.htm
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