Scientists funded by the MRC, Breast Cancer Now and
other collaborators have developed an innovative
imaging technique that could predict whether breast
cancer will spread to the lung.
In the study, published in Theranostics, researchers
have demonstrated in mice that a new non-invasive
imaging method can be used to detect changes in the
lungs that signal breast cancer may soon spread
there – before any metastases are visible.
If validated in humans, this approach could enable
patients to be offered more intensive therapy
earlier, to potentially prevent breast cancer
spread.
Previous research has shown that the gathering of a
special type of immune cell called ‘myeloid-derived
suppressor cells’ (MDSCs) – in locations such as the
lung – prepares the ground for breast cancer
metastasis, by suppressing the local immune system
and promoting the formation of new blood vessels
(angiogenesis).
Researchers at King’s College London – in
collaboration with teams at University College
London and the University Hospital Muenster in
Germany – have now developed a radioactive ‘tracer’
molecule to detect MDSCs accumulating in the lung in
preparation for the arrival of breast cancer cells
and the formation of metastases.
MDSCs are known to release a protein duo ‘message’
called S100A8/A9 which instructs the cells to gather
in the lungs.
The gathering of these MDSCs in the lung causes
inflammation, which makes it a favourable location
for cancer cells to metastasise to.
The research teams – led by Dr Michel Eisenblätter
and Dr Fabian Flores-Borja at King’s College London
– hypothesised that, by making S100A8/A9 visible, it
could be possible to identify when the lungs were
being prepared for colonisation by breast cancer
cells.
To test this theory, they developed a ‘tracer’
antibody able to attach itself to S100A8/A9, that
can be detected using a special scan called SPECT
(single photon emission computed tomography) – a 3D
gamma-ray scanner.
The tracer releases radiation which can be
distinguished by the SPECT scanner, highlighting
areas where S100A8/A9 molecules, and MDSCs, are
accumulating.
The researchers tested the tracer with triple
negative breast cancer cells that had been implanted
in mice, and were able to show – using a miniature
SPECT scanner – that the ‘tracer’ lit up the lungs
of mice well before any tumour cells were visible in
the lung.
Furthermore, the tracer could distinguish between
highly aggressive breast cancer with a high tendency
to spread to the lung and tumours without metastatic
potential.
Currently, to assess the risk of a patient’s breast
cancer spreading, doctors use tools based upon the
features of the primary tumour, such as tumour size
and whether it has already invaded nearby lymph
nodes.
With this early-stage study demonstrating the
technique to be effective in mice, further studies
are now required to develop a more effective
‘tracer’ molecule – better suited for use in humans
– to be tested in clinical trials in future.
This work was also supported by the National
Institute for Health Research Biomedical Research
Centre at Guy's and St Thomas' NHS Foundation Trust
and King's College London, KCL and UCL Comprehensive
Cancer Imaging Centre, the German Research
Foundation, Cancer Research UK, and the Engineering
and Physical Sciences Research Council (EPSRC). The
SPECT scanning equipment at KCL was funded by the
Wellcome Trust.
For more information
Visualization of Tumor-Immune Interaction -
Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic
Niche Establishment
Eisenblaetter M, Flores-Borja F, Lee JJ, Wefers C,
Smith H, Hueting R, Cooper MS, Blower PJ, Patel D,
Rodriguez-Justo M, Milewicz H, Vogl T, Roth J, Tutt
A, Schaeffter T, Ng T.
Theranostics 2017; 7(9):2392-2401.
doi:10.7150/thno.17138
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Mrc Medical Research Council
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King’s College London
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University College London
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Münster University Hospital (UKM)
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