First step of breast cancer metastasis halted in mice

Washington, Dec. 13: Researchers have identified a unique class of breast cancer cells that lead the process of invasion into surrounding tissues, while claiming that because invasion is the first step in the deadly process of cancer metastasis, they may have found a weak link in cancer’s armor and a possible new target for therapy.

Cell biologist Andrew Ewald at Johns Hopkins said metastasis is what most threatens breast cancer patients, and they have found a way to stop the first part of the process in mice.

Before metastasis occurs, single cells on the edge of a tumour, termed leader cells, form protrusions into the surrounding tissue, Ewald said. If the conditions are right, the leader cells act as guides, with many tumour cells following behind, as they escape the confines of the tumour into the healthy tissue beyond.

Beginning with the idea that some cells in the tumour might be more invasive than others, Ewald’s team grew mouse tumours in the laboratory in special 3-D gels that mimic the environment that surrounds breast tumours in human patients.

Kevin Cheung, M.D., a medical oncology fellow in the Ewald lab, observed that the cancer cells infiltrated the gels in groups, with a few cells out in front and the rest following behind.

Looking for a molecular cause for the apparent “leadership” seen in the initiating cells, Cheung searched for proteins that were uniquely present in the leader cells. They identified one protein, cytokeratin 14, or K14, that was present in almost all leader cells but was very rare in the noninvasive parts of the tumour.

When the team looked at tumours from mice that had other types of breast cancer- some more prone to invasion and others less prone- all had leader cells containing K14. The more invasive a tumour was, the more cells with K14 it had.

Cheung said their research showed that the most invasive cells in breast tumours express K14 across all types of breast cancer.

The study was published in the journal Cell. (ANI)