Less 'sticky' cells become more cancerous

Date:
August 25, 2020
Source:
Universita"t Leipzig
Summary:
Researchers have investigated the structure of tumor tissue and
the behavior of tumor cells in detail, gaining important insights
that could improve cancer diagnosis and therapy in the future.



FULL STORY ==========================================================================
In cooperation with colleagues from Germany, Italy and the Netherlands, researchers at Leipzig University have investigated the structure of
tumour tissue and the behaviour of tumour cells in detail, gaining
important insights that could improve cancer diagnosis and therapy in
the future.


==========================================================================
They found out that during tumour development the way cells move
can change from coordinated and collective to individual and chaotic
behaviour. They have just published their research findings in the
journal Nature Cell Biology.

The paper was supervised by tumour biologist Professor Peter Friedl of
Radboud University in Nijmegen, the Netherlands, in cooperation with the research groups headed by Professor Josef A. Ka"s (Leipzig University), Professor Andreas Deutsch (TU Dresden) and Professor Stefano Zapperi (University of Milan). The scientists studied biological changes that
cells usually undergo as cancer develops. The most typical of these is
the degradation of the epithelial adhesion molecule E-cadherin. In other
words: the cells become less "sticky." The researchers showed that this degradation is accompanied by a change in the type of mobility in the
tissue. Cells that are more cancerous can move freely past others of
their kind, while the epithelial cells are "trapped" by their neighbours.

"It has long been assumed that the reduction in cell 'stickiness' during
tumour development increases the mobility of these cancer cells. Our international team was able to confirm this fundamental assumption
and show that a dense environment can still hold cancer cells back,"
said Professor Ka"s. In his view, it is clear that tumour invasion is
strongly influenced by the local environment: cells acting individually
can also move in groups if this reduces the resistance of the surrounding tissue. Both types of cell movement led to metastases in the researchers' experiments.

Most cancers are carcinomas that develop from epithelial tissue that
covers and separates the organs. Its functions include protection and
support. Immobile under healthy conditions, cells in this epithelium
are a standard example in new research into "cell jamming," a field
which is currently developing rapidly. This immobility is explained by
the fact that the cells are in each other's way -- similar to cars in a
traffic jam or individual grains in a pile of sand. And to metastasise,
cancer cells need the ability to move through the body. Their phenotype
changes during tumour development, moving away from epithelial behaviour.

In experiments on tumour cells taken from patients, the researchers found
that cancer cells spread in different ways in different environments:
cells with an epithelial phenotype remained in a closed network, in
which their movements were coordinated and collective. Less "sticky"
cells in turn became more cancerous, with their cohesion reducing and
movements growing more fluid.

Individual, less "sticky" cells separated into the surrounding
tissue. "This only happens if this tissue is not too dense. This movement
is not coordinated, in step, as it would be in cells with an epithelial phenotype, but random and not coordinated with adjacent cells," said
doctoral researcher Ju"rgen Lippoldt from Leipzig University. "In
order to turn this understanding into an advantage for cancer patients,
further research is needed to find out which migration method can lead
to metastases under which circumstances."

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


========================================================================== Journal Reference:
1. Olga Ilina, Pavlo G. Gritsenko, Simon Syga, Ju"rgen Lippoldt,
Caterina A.

M. La Porta, Oleksandr Chepizhko, Steffen Grosser, Manon Vullings,
Gert- Jan Bakker, Jo"rn Starruss, Peter Bult, Stefano Zapperi,
Josef A. Ka"s, Andreas Deutsch, Peter Friedl. Cell-cell adhesion
and 3D matrix confinement determine jamming transitions in breast
cancer invasion.

Nature Cell Biology, 2020; DOI: 10.1038/s41556-020-0552-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200825110656.htm

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