Discovery may lead to ‘smart’ therapies for breast, ovarian cancer

Vancouver, BC – A team of researchers at the University of British Columbia have found that a protein called podocalyxin – which the researchers had previously shown to be a predictor of metastatic breast cancer – changes the shape and adhesive quality of tumour cells, affecting their ability to grow and metastasize.

The discovery demonstrated that the protein not only predicted the spread of breast cancer cells, it likely helped to cause it. The findings were recently published online by the Public Library of Science.

We believe weve found a new important culprit in metastatic breast cancer, which opens up an entirely new avenue of cancer research, says Calvin Roskelley, an associate professor of cellular and physiological science who specializes in breast cancer and is co-senior principal investigator. The culprit is hiding in plain sight on the surface of tumour cells, so we are now developing ‘smart’ molecules to block its function. The ultimate goal is to generate new targeted, non-toxic treatments – very different from the standard ‘slash and burn’ chemotherapy.

The researchers found that podocalyxin significantly expands the non-adhesive face of cells, allowing individual cells to brush aside adhesion molecules situated between tumour cells. The freed cells then move away from the original site to form new tumours at other sites. Also, the protein causes tumour cells to sprout microvilli, or hair-like projections, that may help propel cancer cells to other sites.

In addition, when the protein expands the non-adhesive face of cells it drags along with it a second protein called NHERF-1 – a protein shown by others to be implicated in cell growth and invasion. The researchers now believe the mechanism applies to difficult-to-treat invasive breast and ovarian cancers.

Were now tapping into what causes the characteristic cell shape changes seen in cancerous tumours and possibly how these cells grow and metastasize. It gives us a whole new target for therapy, says Kelly McNagny, associate professor of medical genetics and stem cell expert, who is co-senior principal investigator. If we can block the protein, we may be able to stop the spread of cells.

Post-doctoral fellow Julie Nielsen, of UBCs Biomedical Research Centre, and PhD student Marcia Graves of the department of cellular and physical sciences, were instrumental in designing and executing the research experiments, he adds.

Next steps involve advancing the research in animal models, designing antibodies to block the function of the protein and working with the UBC-based Centre for Drug Research and Development to identify new therapies to combat metastasizing cancer.