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Cancer Cells Stopped from Metastasizing along Highways in Tumors

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Researchers at the University of Minnesota have developed a technique to stop cancer cells from moving and metastasizing. The discovery could have a major impact on millions of people undergoing therapies to prevent the spread of cancer within the body, according to the scientists.


It’s been known for years that tumors have patterns that are like little “highways” that cancer cells use to move within the tumors and ultimately toward blood vessels and adjacent tissue to invade the body. Patients who have high numbers of these patterns in their tumors have a lower chance of surviving the cancer.



What the researchers haven’t been able to figure out until now is how the cells recognize these patterns and move along them.


In this study (“Bimodal sensing of guidance cues in mechanically distinct microenvironments”), published in Nature Communications, the University of Minnesota team examined in the lab how breast cancer cells moved and used medicines to try to stop the cells. When they stopped the mechanisms that serve as the motor of the cells, the cells changed the way they moved to an oozing-like motion, almost like a blob.


“In contractile cells, guidance sensing is strongly dependent on formins and FAK signaling and can be perturbed by disrupting microtubule dynamics, while low traction conditions initiate fluidic-like dendritic protrusions that are dependent on Arp2/3. Concomitant disruption of these bimodal mechanisms completely abrogates the contact guidance response. Thus, guidance sensing in carcinoma cells depends on both environment architecture and mechanical properties and targeting the bimodal responses may provide a rational strategy for disrupting metastatic behavior.”


Ninety percent of cancer deaths are due to the cancer spreading throughout the body, noted Dr. Provenzano, adding that putting the brakes on cancer cell movement would allow physicians the time to use other therapies to improve survival rates of patients.


The researchers studied the cells in the lab in two-dimensional, engineered microenvironments, that are almost like a microchip with cells. These microenvironments mimicked how the cells behave as they do in a tumor and allowed researchers to speed up their research.


“By using these controlled network microenvironments, we were able to test hundreds of cell movement events in hours compared to one or two in the same time frame by imaging a tumor,” pointed out Erdem Tabdanov, Ph.D., a University of Minnesota biomedical engineering postdoctoral researcher and first author of the study.


The next steps for the research team are to expand the types of cancers studied and begin animal trials. Within a few years, the researchers hope to move to clinical trials in humans. They will also study how the medicines interact and what side effects may result.


“Ultimately, we’d like to find ways to suppress cancer cell movement while enhancing immune cell movement to fight the cancer,” said Dr. Provenzano.

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