Activation of a specific intracellular signalling cascade determines whether cancer cells spread as single cells or as a collective unit, and whether they invade via the lymph system or blood reports a study in this week's Nature Cell Biology. The spread of solid tumours accounts for cancer morbidity and therefore this work is of key interest for therapeutic intervention and drug design.
Erik Sahai and colleagues non-invasively visualized the movement of fluorescently labelled breast cancer cells inside living mice, using highly sensitive cameras. They found that whereas some tumour cells move alone, others move more slowly in groups. Though the cytokine growth factor TGF-beta is known to increase tumour cell motility, the team found that TGF-beta signalling is only active in singly moving cells and not in collectively moving cells. Surprisingly, both types of migration led to the spread of cancer, though to different sites. Cells lacking TGF-beta signalling moved collectively, spreading only to lymph nodes. Conversely, increased TGF-beta signalling led to increased dissemination of singly moving cells into blood, but also prevented the spread of cancer to the lungs. Therefore, the TGF-beta pathway needs to be activated for single-cell motility, but then needs to be shut off for cancer to spread to the lungs.
These findings illustrate how different cells in a tumour can have different signalling properties, and may help in the design of drugs that prevent cancer spreading from organ to organ.