An interaction between two proteins enables cancer cells
to use the physical forces of healthy cells to start spreading to
other parts of the body.
The finding by researchers from the Francis Crick Institute in
London and the Institute for Bioengineering of Catalonia (IBEC) in
Barcelona is published in the journal Nature Cell Biology.
The process by which cancer cells separate from the original
tumour to form new tumours in other organs or tissues of the body
is called metastasis, and it is responsible for the majority of
deaths in patients with cancer.
Many cancers initially have a very limited ability to invade the
tissue around them. But over time they find the mechanism to do so,
increasing the aggressiveness of the cancer.
The British and Spanish research team identified a mechanism by
which cancer cells manage to escape the tumour to promote
metastasis. They revealed that tumour cells can reprogramme their
healthy neighbours, dragging them out of the tumour and into other
tissues.
The victims of this 'kidnapping' are fibroblasts, a cell type
that is responsible for the synthesis and organization of the
extracellular matrix - the scaffolding in which cells reside and
which helps give structure to tissues in the body.
"Fibroblasts are professionals in maintaining healthy tissues,
and are able to create tunnels in the tissues to travel through,"
says Anna Labernadie of IBEC and first author of the study. "They
use this ability to restore the tissues when we suffer an
injury."
The researchers, led by Xavier Trepat at IBEC and Erik Sahai at
the Crick, showed that cancer cells use the mobility of fibroblasts
to escape the tumour and travel through tissues. The surrounding
tumour, or stroma, modifies the fibroblasts and uses them for the
invasion into other tissues. From this point, the fibroblasts start
to serve the cancerous cells, tracing paths for them through the
extracellular matrix surrounding the tumour.
The scientists have now shown that fibroblasts not only create
tunnels beyond the stroma, but exert physical forces to drag cancer
cells through these tunnels, promoting the invasion of healthy
tissue.
"It's like a train: the fibroblasts are locomotives and the
cancer cells are wagons," says Labernadie.
The group were able to identify the mechanism by which cancer
cells stick to fibroblasts and move together. It is down to an
interaction between two different proteins, one located on the
surface of cancer cells called E-cadherin, and another expressed on
the surface of fibroblasts, called N-cadherin.
"These proteins are the nanoscale hooks that enable cells to
join together," says Xavier Trepat of IBEC. "Until now, we knew
very little about this interaction.
The researchers used cells and tissues obtained from patients
with lung and skin cancer. "We identified this mechanism in very
different tumours, which suggests that it may be universal,"
stresses Xavier. "Because of the poor prognosis for patients who
have suffered cancer metastasis, identifying the mechanisms that
promote tumour growth can help us find ways to stop it."
The paper, A mechanically active heterotypic
E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer
cell invasion, is published in Nature Cell
Biology.