Stem cells key in cancer spread

11 Oct 2007
Bone marrow stem cells have been found to promote the spread of breast cancer to other areas, according to scientists working in a number of institutions in Massachusetts.

The research, published this month in Nature, found that mesenchymal, or multipurpose, stem cells (MSCs) were influenced by breast cancer cells to produce a chemical which promotes further invasion and spread of cancerous tumours.

The study, lead by postdoctoral researcher Antoine Karnoub, gives potential for a treatment designed to prevent the spread of breast cancer.

Mice and cultured cells were used to test the relationship between the chemical, known as CCL5, and tumour spread, with measurements by a number of methods including immunohistochemistry, cytokine array and gene expression analysis.

MSCs have been previously observed to change their format when in proximity to breast cancer cells, where they integrated into the supportive framework of the tumour’s stroma.

However, the involvement of MSCs in the perturbation of tumour behaviour had yet to be addressed. It was demonstrated that MSCs from human bone marrow, when introduced adjacent to dormant breast cancer cells, caused them, to spread (or metastasise) more frequently than usual. This occurred when the cell mixture was introduced into a subcutaneous site.

The breast cancer cells stimulate secretion of the chemokine CCL5 (also called Rantes) from MSCs, which in turn affects the signalling of the cancer cells such that motility, invasion and metastasis are enhanced.

The potential for therapy lies with the fact that this enhancement of the ability to spread is reversible; dependent on CCL5 signalling. If CCL5, or the part of the cell that is receptive to it, can be targeted using drugs, the signalling can be altered or blocked and spread may be prevented.

This research is novel in its concentration on the material between the cells, rather than the cells themselves.