Cell adherence may predict metastasis potential of cancer cells

In metastasis, cancer cells break away from the primary site of the tumor and travel through the blood or lymphatic system to more distant parts of the body. However, only a small number of malignant cells have the ability to form secondary tumors. New research may have found a way to identify these cells.

Based on the latest available data from the National Cancer Institute, almost 40 percent of the United States population will receive a cancer diagnosis at one point in their lives.

Some of these diagnoses progress into a metastasis, which often results in death. The yearly cancer mortality rate is currently estimated at 171.2 deaths per 100,000 men and women.

Metastasis is the process by which cancer cells spread to other parts of the body - such as the lymph nodes, tissues, or other organs - and form new tumors. However, only a small fraction of the cancerous cells have the potential to spread.

A team of researchers, led by Adam Engler of the University of California in San Diego, noticed that there are not many biological markers available that help to identify metastatic cells, and he consequently set out to study the probability that a cell would develop into a secondary tumor. The study - published in the Biophysical Journal - built on previous research that suggested the strength with which cells could attach to the tumor tissue around them could be a valid biophysical marker that predicts secondary cancer development.

Study co-author Afsheen Banisadr, a Ph.D. student in the Engler laboratory at the University of California, explains the motivation behind the study:

"We reasoned that understanding adhesive heterogeneity within an invasive population may improve our ability to physically monitor cancer cells and predict invasive behavior."

Low cell adherence may indicate that a tumor is more likely to spread

To test their hypothesis, the researchers built a spinning disc designed to measure how quickly and strongly breast and prostate cancer cells could adhere to a coverslip covered in extracellular matrix proteins, which are molecules that offer structural support to the cells nearby and guide their growth and development.

The coverslip was then attached to a spinning rod, and researchers applied force across the cell population. Finally, they measured the shear these cells required in order to fall off the extracellular matrix protein-coated coverslip.

What they found was that metastatic cells are remarkably more heterogenous in their adhesion strength when compared with non-metastatic ones. Cells that adhere very strongly tend to migrate less, just like non-metastatic cell lines. Overall, this suggests that the strength of adhesion might function as a very accurate biological marker of metastatic cells.

"There is no common biological marker that says that a tumor is more likely to spread," says Engler. "However, our device shows that there may, in fact, be a physical marker that is predictive of the likelihood of spreading."

In the future, using a mouse model, the researchers hope to test whether cells with low adherence form tumors much quicker than the general population of cancerous cells. If their hypothesis is confirmed, the scientists will go on to investigate the tissue around tumors in both mice and humans in order to find these poorly adhering cells, and to study their correlation with survival rates 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."

Pranjali Beri, Ph.D., study co-author

Ultimately, the scientists hope to be able to use this information to make earlier predictions regarding whether patients require more aggressive forms of therapy. "However, patients should realize that the timing for these results to hit even the initial clinical trials is several years away," Engler says.

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