Breast cancer cells enticed to spread by "tumorous environment", genetic changes

A new study from Johns Hopkins researchers suggests that the lethal spread of breast cancer is as dependent on a tumour's protein-rich environment as on genetic changes inside tumour cells.

In a report in the Proceedings of the National Academy of Sciences in September, the scientists conclude that a molecular signal in the protein meshwork surrounding the breast cancer cells may provide the critical trigger to initiate the life-threatening process of metastasis to distant sites in the body.

Moreover, their experiments suggest that the environment surrounding a tumour can even coax healthy breast cells to invade surrounding tissue just as cancer cells do, and that a healthy environment can cause cancer cells to stay put and not spread as they usually do.

''The most dangerous aspect of breast cancer is its ability to spread to distant sites, and most tumours are initially unable to do that,'' says Andrew Ewald, PhD, assistant professor of cell biology at the Johns Hopkins School of Medicine and member of the Institute for Basic Biomedical Sciences' Center for Cell Dynamics. Learning more specifically what triggers metastases may provide additional targets for preventing and treating the malignant process that causes cancer deaths, Ewald adds.

It's widely accepted that cancers acquire the ability to spread through the gradual accumulation of genetic changes, and experiments have also shown that these changes occur in parallel with changes in the protein content and 3-dimensional patterning of the protein meshwork that creates their immediate surroundings. What has been unclear is whether those immediate surroundings play a role in initiating and encouraging cancer's spread, or whether they are more ''effect'' then ''cause.''

To sort out the contributions of both the genetic changes and the environment, Ewald's team separated tumor cells from their surroundings by taking fragments of human breast tumours and embedding them in two different commercially available 3-D gels, one that mimics the protein meshwork surrounding healthy mammary tissue and another that mimics tumorous mammary tissue.