New cancer-fighting strategy would harden cells to prevent metastasis

Present therapies to treat cancer focus on killing tumor cells, so that there is no chance for them invading other parts of the body. In a new study by the researchers at the John Hopkins researchers have proposed a different strategy. The report on the study appeared in the early edition of the Proceedings of the National Academy of Sciences which reveals the scientists have found a way of subtly hardening cancer cells so that they cannot invade into new areas of the body. They devised a way which will help in screening such compounds for the desired effect and have even identified a compound that looks promising in fighting pancreatic cancer.

Douglas Robinson, Ph.D., a professor of cell biology in the Institute for Basic Biomedical Sciences at Johns Hopkins University School of Medicine said that with their novel approach to cancer therapy, the way we fight this disease could be revolutionized. It can also help in identifying drugs for many other diseases.

Robinson said that the idea of the project came to him in 1997. He was then a postdoctoral fellow. He said that he had the idea that if we can understand how a cell divides into two better, it could shed some light on how cells change shape in general. Changes in cell shape eventually figure into conditions from cancer to chronic obstructive pulmonary disease to degenerative nerve diseases. He was of the opinion that the compounds that affect cells shape might turn out to stall disease progress.

The lead author of this study Alexandra Surcel, Ph.D., joined Robinson’s laboratory as a postdoctoral fellow in the year 2008. He started his work on a screen for molecules that tweak cell shape. Surcel explained that this screen was different as it is based on the end result for a whole cell. In this case, he chose the amoeba Dictyostelium, which closely resembles a number of mammalian cell types.  The cells were treated with a molecule after which, Robinson’s team looked for out-of-the-ordinary numbers of cells with two or more nuclei. Typically, Dictyostelium have two nuclei only when they are likely to be in the process of dividing into two daughter cells. So, if there are a high proportion of cells with more than one nucleus, it should be safely concluded that the molecule has played havoc with the process of cell division.

While a screen of thousands of molecules showed the effect the team was looking for, on further study they found that one of them, 4-HAP, affected myosin II, a building block of the cell skeleton. The group of researchers identified changes in the amount of myosin II in pancreatic cancer cells as they spread from the original tumor into other areas of the body, a crucial step in progression of the disease.

The 4-HAP was tested on lab-grown pancreatic cancer cells and they found that it affected the myosin in their skeletons in such a way that made them harder. Surcel says that since the cancer cells are relatively soft, invading cancer cells slip through healthy cells of the body and make colonies of malignant cells in new areas of the body.

Further investigations are needed to find out if this strategy would work in humans. Presently, the team is testing 4-HAP in mice. The drug is already in use in some countries for treating jaundice. So, in the eventuality that it is successful against pancreatic cancer, it could potentially make it to market relatively quickly. Whether that happens or not, the study has already identified the great potential this drug has.

References

https://www.eurekalert.org/pub_releases/2015-01/jhm-ncs012015.php

https://www.sciencedaily.com/releases/2015/01/150120142658.htm