11 August 2014
Certain cell mechanics may hold the key to how cancer spreads and recurs, according to new research from the University of Illinois.
The results, which appear in the journal Nature Communications, noted that some cancer cells can cause a cancer to spread to other organs through metastasis, or evade treatment to resurface after a patient is thought to be in remission.
Along with colleagues in China, the Illinois team found that these so-called tumor-repopulating cells may lurk quietly in stiffer cellular environments, but thrive in a softer space.
In a previous study, a group from the university published a method for selecting tumor-repopulating cells (TRCs) from a culture and isolated and studied TRCs from melanoma to see how the mechanical environment around the cells affected their ability to multiply and cause new tumors.
The researchers grew the cells on gels of different stiffnesses - some very soft and some more firm - to mimic different types of tissues in the body.
What they found surprised them, according to study leader Ning Wang, the Leonard C. and Mary Lou Hoeft professor in engineering and professor of mechanical science and engineering at the University of Illinois.
He stated: "What causes relapse is not clear. Why are there a few cells left that can come back stronger? We thought cancer cells may have some properties in common with stem cells, which allows them to metastasize to different tissues. Normally, if you take a liver cell and put it in your lung, it will die. But an undifferentiated cell will live."
He noted that the TRCs placed in very soft gels grew and multiplied, as expected, but the cells placed on stiffer gels did not proliferate, nor did they die; they became dormant, and only when later transferred the dormant TRCs to a soft gel did they 'wake up' and begin to multiply and spread.
He speculated that the properties of dormancy and reawakening when the mechanical environment is more inviting may explain why soft tissues, such as the brain or lungs, are most vulnerable to metastasis.
Professor Wang added: "We have many different types of organs where solid tumors originate, but if you look at the metastasized sites, the majority are in soft tissues. Brain, lung, liver and bone marrow, all soft. So it may not be coincidence. We need to do more research."
Professor Wang and his colleagues now hope to tackle the question of what makes TRCs so resistant to drugs; a trait that makes recurrent cancer much harder to treat.
Unlocking this puzzle may help doctors fight recurrent cancer, although he hopes that understanding how TRCs work can lead to treatments that prevent metastasis in the first place.
He concluded "The key issue in this paper is outlining the mechanisms that control how TRCs proliferate. The importance of knowing these mechanisms is that we now have targets that we didn’t have before, specific targets for new types of drugs that will interfere with this renewal pathway. It could give us a new avenue for treatment and preventing relapse."
Posted by Jeanette Royston
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