Acoustic device that separates tumor cells from blood cells could help assess cancer’s spread.
Researchers from MIT, Pennsylvania State University, and Carnegie Mellon University have devised a new way to separate cells by exposing them to sound waves as they flow through a tiny channel. Their device, about the size of a dime, could be used to detect the extremely rare tumor cells that circulate in cancer patients’ blood, helping doctors predict whether a tumor is going to spread.
Separating cells with sound offers a gentler alternative to existing cell-sorting technologies, which require tagging the cells with chemicals or exposing them to stronger mechanical forces that may damage them.
To sort cells using sound waves, scientists have previously built microfluidic devices with two acoustic transducers, which produce sound waves on either side of a microchannel. When the two waves meet, they combine to form a standing wave (a wave that remains in constant position). This wave produces a pressure node, or line of low pressure, running parallel to the direction of cell flow. Cells that encounter this node are pushed to the side of the channel; the distance of cell movement depends on their size and other properties such as compressibility.
However, these existing devices are inefficient: Because there is only one pressure node, cells can be pushed aside only short distances.
The new device overcomes that obstacle by tilting the sound waves so they run across the microchannel at an angle — meaning that each cell encounters several pressure nodes as it flows through the channel. Each time it encounters a node, the pressure guides the cell a little further off center, making it easier to capture cells of different sizes by the time they reach the end of the channel.
By 2050, the number of people over the age of 80 will triple globally. These demographics could come at great cost to individuals and economies.
The problems of old age come as a package. More than 70% of people over 65 have two or more chronic conditions such as arthritis, diabetes, cancer, heart disease and stroke.
Restricting calorie intake in mice or introducing mutations in nutrient-sensing pathways can extend lifespans by as much as 50%. And these ‘Methuselah mice’ are more likely than controls to die without any apparent diseases.
The current tools for extending healthy life — better diets and regular exercise — are effective. But there is room for improvement, especially in personalizing treatments.
Longevity pathways identified in model organisms seem to be conserved in humans and can be manipulated in similar ways. Genetic surveys of centenarians implicate hormonal and metabolic systems. Long-term calorie restriction in humans induces drastic metabolic and molecular changes that resemble those of younger people, notably in inflammatory and nutrient-sensing pathways.
Several molecular pathways that increase longevity in animals are affected by approved and experimental drugs. Cancer and organ-rejection drugs such as rapamycin extend lifespan in mice and worms by muting the mTOR pathway, which regulates processes from protein synthesis to cell proliferation and survival. The sirtuin proteins, involved in a similar range of cellular processes, are activated by high concentrations of naturally occurring compounds (such as the resveratrol found in red wine) and extend lifespan in metabolically abnormal obese mice. A plethora of natural and synthetic molecules affect pathways that are shared by ageing, diabetes and metabolic syndrome. (Luigi Fontana, Brian K. Kennedy, Valter D. Longo, Douglas Seals& Simon Melov, Nature 511, 405–407 (24 July 2014) doi:10.1038/511405a)
Cell membranes are covered with sugar-conjugated proteins. New findings suggest that the physical properties of this coating, which is more pronounced in cancer cells, regulate cell survival during tumour spread.
The cell membrane serves as a signalling interface that allows cells to exchange information with their environment. It is constructed from lipids and contains both transmembrane and lipid-tethered proteins, which can be further modified through the covalent addition of sugars to build glycoproteins. Cancer cells frequently have higher levels of glycoproteins, such as mucin-1, than do healthy cells, and individual glycoproteins can transduce environmental signals that directly promote malignancy. However, glycoproteins also collectively organize into a glycocalyx.
Integrins are transmembrane receptors that bind extracellular matrix (ECM) proteins and are key interpreters and integrators of both the biochemical composition and the mechanical properties of the extracellular space. Cells with a thick glycocalyx are more efficient at receiving cell-survival signals through integrins, owing to the kinetic-trap properties of the glycocalyx. This may facilitate metastatic spread by enabling cancer cells to survive in the varied tissue and fluid environments they must traverse to colonize distant organs.
Integrin-based cell-matrix signalling is important for many steps in metastasis, including the migration of cancer cells out of the primary tumour and through the ECM, their entry into the vasculature, survival in the circulation, adhesion to the vessel wall, exit from the vasculature, and migration to and proliferative expansion in a distant organ. By reducing the rate of integrin binding and promoting clustering at existing adhesion sites, bulky glycoproteins act to promote a stable interaction between the cancer cells and the ECM.
We expect that the optimal glycocalyx thickness for supporting different aspects of cancer-cell behaviour, including invasion, vascular spread and metastatic colonization, varies. But how cancer cells adapt their glycocalyx to the diverse surroundings that they experience during metastasis is an interesting open question. Andrew J. Ewald & Mikala Egeblad, Nature511,298–299(17 July 2014)doi:10.1038/nature13506)