It's a high-pressure environment within solid tumours.

Abnormal blood and lymphatic vessels cause fluids to accumulate, and the uncontrolled proliferation of cancer cells within limited space leads to the buildup of what is called solid stress.

Both types of pressure can interfere with the effectiveness of anticancer treatments, but while strategies have been developed that reduce fluid pressures, little has been known about the impact of solid stress or potential ways to alleviate it.

Now a Massachusetts General Hospital (MGH) research team has identified factors that contribute to solid stress within tumours, suggesting possible ways to alleviate it, and has developed a simple way to measure such pressures.

"Traditionally cancer research has focused on cancer cells and, more recently, on the biochemical microenvironment of tumours," says Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and senior author of the study in Proceedings of the National Academy of Sciences. "Our work shows that the physical or mechanical microenvironment plays an equally important role in tumor progression and treatment resistance."

Jain and his colleagues have been leaders in understanding the impact of elevated fluid pressures that make it difficult for drugs to enter and permeate tumors.

Their work showed that fluid pressures are relieved when antiangiogenesis drugs normalise the abnormal blood vessels characteristically found within solid tumours, improving the effectiveness of other anticancer therapies. But that approach can only work if vessels have not been squeezed shut by solid stress in surrounding tissues. In recent studies Jain's team showed that solid stress also increases the invasiveness of cancer cells.

The current study was designed to develop techniques that measure solid stress in tumours, to identify factors that contribute to the generation of this solid stress and to determine whether previously compressed blood vessels would open when stress-inducing components were depleted. Based on predictions from mathematical models, the MGH-based team developed a remarkably simple way to measure solid stress within tumor tissues.

In experiments using both tumours experimentally grown in mice and tumours removed from human patients, the researchers found that, when a solid tumour is cut in two, each segment begins to swell along the sliced surface, releasing stored solid stress. In contrast, when a sample of normal tissue is cut in two, the separated halves of tissue retain their size and shape (links to video files below). Measuring the extent of shape relaxation along with other mechanical properties of tumour tissue enabled calculation of the amount of solid stress within a tumour sample.

Source: Massachusetts General Hospital