How do tumor cells divide in the crowd?

Date:
September 2, 2020
Source:
Technische Universita"t Dresden
Summary:
Scientists studied how cancer cells are able to divide in a crowded
tumor tissue and connected it to the hallmark of cancer progression
and metastasis, the epithelial-mesenchymal transition (EMT).



FULL STORY ========================================================================== Scientists led by Dr. Elisabeth Fischer-Friedrich, group leader at the Excellence Cluster Physics of Life (PoL) and the Biotechnology Center TU Dresden (BIOTEC), studied how cancer cells are able to divide in a crowded tumor tissue and connected it to the hallmark of cancer progression and metastasis, the epithelial-mesenchymal transition (EMT).


==========================================================================
Most animal cells need to become spherical in order to divide. To achieve
this round shape, the cells must round up and deform their neighboring
cells. In a growing tumor tissue, the tumor cells need to divide in an environment that is becoming more crowded than the healthy tissue. This
means that the dividing tumor cells likely need to generate much higher mechanical forces to round up in such a densely packed surrounding. Yet,
tumor cells seem to be adapted to overcome these difficulties. Scientists
led by Dr. Elisabeth Fischer-Friedrich were curious how do the tumor cells
gain this enhanced ability to deal with the crowded tumor environment?
The researchers found that the EMT could be one of the answers. What
is it exactly? "EMT or epithelial-mesenchymal transition is a hallmark
of cancer progression," says Kamran Hosseini, PhD student who performed
the experiments.

It is a cell transformation during which tumor cells lose their asymmetric organization and detach from their neighbors, gaining the ability to
migrate into other tissues. This, together with other factors, allows
tumors to metastasize, i.e., move into the blood and lymphatic vessels
and ultimately colonize other organs.

"So far, EMT has been mainly linked to this enhanced cell dissociation
and cell migration. Our results suggest that EMT might also influence
cancer cells by promoting successful rounding and cell division. These
results point towards a completely new direction of how EMT could promote metastasis of carcinoma in the body," explains Kamran Hosseini.

Just as we test the ripeness of the fruits by squeezing them gently
with our hands, the scientists examined the mechanical properties of
individual human cells. Except, they squished the cells using an atomic
force microscope. This state-of-the-art setup measured properties such
as cell stiffness and cell surface tension before and after the EMT. In addition, the group of Dr.

Elisabeth Fischer-Friedrich in collaboration with Dr. Anna Taubenberger (BIOTEC, TU Dresden) and Prof. Carsten Werner (IPF, Dresden) cultured
mini- tumors and trapped them inside elastic hydrogels to check how
mechanical confinement affects cell rounding and division of tumor cells.

The authors identified changes in rounding and growth of the tumor. EMT influenced the cancer cells in two contrasting ways. The dividing
tumor cells became stiffer while surrounding non-dividing cells became
softer. Furthermore, the researchers found hints that the observed
mechanical changes could be linked to the increased activity of a protein called Rac1, a known regulator of the cytoskeleton.

"Our findings will not only provide important results to the field of
cell biology but may also identify new targets for cancer therapeutics,"
says Dr.

Elisabeth Fischer-Friedrich.

This study was founded by the German Research Foundation (DFG) and
performed in collaboration with the Light Microscopy Facility (LMF) of the
CMCB Technology Platform at TU Dresden. Dr. Elisabeth Fischer-Friedrich
is a core group at the newly formed Physics of Life Cluster of Excellence
(PoL) at TU Dresden.


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


========================================================================== Journal Reference:
1. Kamran Hosseini, Anna Taubenberger, Carsten Werner, Elisabeth
Fischer‐Friedrich. EMT‐Induced Cell‐Mechanical
Changes Enhance Mitotic Rounding Strength. Advanced Science, 2020;
2001276 DOI: 10.1002/advs.202001276 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200902101814.htm

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