Cancer cells spread by detaching and migrating away from the primary
tumor to form a secondary metastatic site. However, only a small subset
of cancer cells from a tumor or even from a cancer cell line is capable
of forming secondary tumors.
Efforts to identify a universal molecular
marker that identifies metastasizing cells across tumor types have been
‘Tumor cells characterized by weak adhesion strength are more likely to migrate and invade other tissues compared with strongly adherent cells.’
How strongly tumor cells adhere to the surrounding tissue could
indicate the likelihood that cancer will spread to other parts of the
body, according to a study published in Biophysical Journal
Using a spinning disc device, the researchers found that tumor cells
characterized by weak adhesion strength are more likely to migrate and
invade other tissues compared with strongly adherent cells. The study
may provide a much-needed marker to identify highly metastatic cells
within a broader tumor cell population.
"There is no common biological marker that says that a tumor is more
likely to spread," says senior study author Adam Engler of the
University of California, San Diego. "However, our device shows that
there may in fact be a physical marker that is predictive of the
likelihood of spreading."
By contrast, some studies have suggested that a biophysical marker - the strength with which cells attach to the surrounding tumor tissue - could indicate the likelihood of secondary tumor development. But
even within an individual tumor, cells exhibit substantial variability
in their adhesive strength.
"We reasoned that understanding adhesive
heterogeneity within an invasive population may improve our ability to
physically monitor cancer cells and predict invasive behavior," says
study co-author Afsheen Banisadr, a Ph.D. student in the Engler lab at
the University of California, San Diego.
To test this idea, Engler's lab teamed up with co-author Thea Tlsty
of the University of California, San Francisco, to build a custom
spinning disc device that could measure the adhesion strength of breast
and prostate cancer cells of varying metastatic potential. The
researchers attached cells to a coverslip coated with extracellular
matrix proteins - molecules that provide structural and biochemical
support to the surrounding cells. Then they mounted the coverslip on a
spinning rod and applied force in a quantifiable and reproducible manner
across the cell population, measuring the shear required to detach the
cells from the extracellular matrix protein-coated coverslip.
Using this spinning disc shear assay, they found that metastatic
cells exhibit remarkable heterogeneity in their adhesion strength,
unlike their non-metastatic counterparts. Strongly adherent metastatic
cells exhibit less migratory behavior, similar to non-metastatic cell
lines. Taken together, the findings suggest that adhesion strength may
serve as a general, highly accurate marker of metastatic cells.
Building on these findings, Engler and his team have developed a
second-generation device that isolates weakly adherent migratory cells.
In future studies, they will test whether these cells, when injected
into mice, will form tumors at a higher rate than a general population
of tumor cells. If this hypothesis is correct, the researchers will then
examine tissues adjacent to tumors in mice and humans to detect these
weakly adherent cells and correlate their concentration to cancer-free
survival times for patients.
"If we find a correlation between low numbers of weakly adherent
tumor cells in the tissue surrounding a tumor and long cancer-free
survival times, we believe that this could serve as an indicator for
metastatic potential of the patient's tumor," says study co-author
Pranjali Beri, a Ph.D. student in the Engler lab at the University of
California, San Diego.
In the future, clinicians could use this device to examine tumor
biopsies and estimate the likelihood of metastasis, using this
information to assess whether patients might need more aggressive
treatment at earlier disease stages. "However, patients should realize
that that the timing for these results to hit even the initial clinical
trials is several years away," Engler says.