| RESEARCH HIGHLIGHTS |


Newton’s laws of motion to a static structure “to create a movie that zooms in on all the jiggling atoms.” They simulated the viral shell, and played


with different components to see what happened with the overall structure. “We used a Franken- stein-style approach to chop off bits of protein from the virus and see how it affected the morphology — a difficult job in the wet lab.”


Surprisingly, the membrane’s curves seemed


to be held in place by scaffolding proteins external to the membrane. And the positioning of envelope and membrane proteins was secured by specific interactions with negatively charged lipids in the fatty membrane, a finding that could be exploited for treatment development. The results have important implications for the fusion process (see image), which Bond and


Verma plan to study in more detail through a larger Singapore-wide collaboration supported by the Ministry of Education. The teams are also expanding their scope to other flaviviruses, including Zika.


1. Marzinek, J. K., Holdbrook, D. A., Huber, R. G., Verma, C. & Bond, P. J. Pushing the envelope: Dengue viral membrane coaxed into shape by molecular simulations. Structure 24, 1410–1420 (2016).


Cancer


BUSTING MYTHS ON TUMOR CELL CLUSTERS


A SURPRISING FINDING SHOWS THAT SOME CLUSTERS OF CELLS COMMONLY FOUND IN THE BLOODSTREAM OF COLORECTAL CANCER PATIENTS ARE ACTUALLY NON-CANCEROUS


In a major debunking of scientific orthodoxy, A*STAR researchers have discovered a new type of tumor-derived cells that are non-can- cerous floating in the bloodstream1. This finding promises to open novel, non-invasive ways to detect and monitor the spread of cancer in the body. For decades, clusters of cells circulating in


the bloodstream of cancer patients have been regarded as invasive cancerous cells shed by the tumor. They have been implicated in spreading cancer to other parts of the body, resulting in secondary tumors that are often harder to kill than the initial tumor. Now, Min-Han Tan of the A*STAR Insti-


tute of Bioengineering and Nanotechnology (IBN) and his co-workers have exonerated some clusters of circulating tumor cells, finding that they are not actually cancerous. The discovery goes against half a century of


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received wisdom that all varieties of circulating tumor cells are malignant. “This was an abso- lutely surprising result,” comments Tan. “When we first set out on this study, we expected to find that these clusters were cancerous.” The researchers used a custom-designed


microdevice, which was developed by Jackie Y. Ying’s team at IBN, to trap cell clusters in blood samples of 80 patients with colorectal cancer (see image). Analysis of the cells’ DNA and RNA revealed that the cells originated from the innermost lining of blood vessels that line the tumor, rather than from the tumor itself. Tan and the team also found that these clusters detached intact from blood vessels near a tumor and were not formed by individual cells coming together in the bloodstream. By monitoring these clusters, doctors should


be able to glean vital information about cancer in other parts of the body during the course of


Clusters of human cells originat- ing from blood vessels captured


from the bloodstream by using a custom-designed microdevice.


treatment. “What I think excites everyone is the chance to measure the vascular health of a tumor non-invasively, which has never hitherto been possible,” explains Tan. “One can imagine administering drugs and evaluating the impact of such agents on the tumor vasculature.” It may even be possible to use the clusters


10µm


to diagnose certain cancers. “Unexpectedly, we found that these clusters commonly occur even in the early stage of colorectal cancer, which opens up an opportunity to investigate using these cell clusters for cancer screening,” adds Tan. In the future, the team intends to study these


circulating cell clusters in other types of cancers. They also plan to develop improved ways to capture and characterize these clusters.


1. Cima, I., Kong, S. L., Sengupta, D., Tan, I. B., Phyo, W. M. et al. Tumor-derived circulating endothelial cell clusters in colorectal cancer. Science Translational Medicine 8, 345ra89 (2016).


A*STAR RESEARCH 51


© 2016 A*STAR Institute of Bioengineering and Nanotechnology


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