How cancer cells break free from tumours

Anne Trafton, MIT News Office

Although tumour metastasis causes about 90 per cent of cancer deaths, the exact mechanism that allows cancer cells to spread from one part of the body to another is not well understood. One key question is how tumour cells detach from the structural elements that normally hold tissues in place, then reattach themselves in a new site.

A new study from MIT cancer researchers reveals some of the cellular adhesion molecules that are critical to this process. The findings, published 9 October in Nature Communications, offer potential new cancer drug targets, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, and leader of the research team.

''As cancer cells become more metastatic, there can be a loss of adhesion to normal tissue structures. Then, as they become more aggressive, they gain the ability to stick to, and grow on, molecules that are not normally found in healthy tissues but are found in sites of tumour metastases,'' says Bhatia, who is also a member of the David H Koch Institute for Integrative Cancer Research at MIT. ''If we can prevent them from growing at these new sites, we may be able to interfere with metastatic disease.''

Lead author of the paper is Nathan Reticker-Flynn, a PhD student in Bhatia's lab. Other authors are former students David Braga Malta and Mary Xu, postdocs Monte Winslow and John Lamar, and research scientist Gregory Underhill. In addition, Richard Hynes, the D K Ludwig Professor of Biology and a member of the Koch Institute, and Tyler Jacks, director of the Koch Institute, are contributing authors on this study.

Losing and gaining adhesion
Cells inside the human body are usually tethered to a structural support system known as the extracellular matrix, which also helps regulate cellular behaviour. Proteins called integrins, located on cell surfaces, form the anchors that hold the cells in place. When cancer cells metastasize, these anchors let go.