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Mice provide clues to how cancer spreads

3D reconstruction a breast tumour

This image shows the cancer cells (green) starting to invade the lymphatic vessels (red). Collagen fibres are shown in blue (Source: Tumour Cell Biology lab, Cancer Research UK )

Scientists studying the spread of breast cancer cells in mice have found a gene signal that controls how the cells move.

The team at Cancer Research UK found that a genetic signal, known as TGF-beta, was crucial to whether cells moved as single entities or in clumps.

TGF-beta signalling is only active in singly moving cells, not in collectively moving cells. And in singly moving cells, the signal is on when they move and off when they stop in a new place to grow, they reported in the journal Nature Cell Biology.

"The results helped us to find the set of genes that are behind the spread of breast cancer - and that the genes need to be first turned on and then off in order for single cancer cells to be able to relocate," says Dr Erik Sahai, head of the tumour cell biology lab at Cancer Research UK's London institute.

Cancer spread

A study published in May 2007 in the Journal of Clinical Investigation found that treating cancer with surgery, chemotherapy or radiation raised levels of TGF-beta and could actually cause tumours to spread.

But as yet, relatively little has been known about how cancer cells spread through the body because it is very difficult to track them when they are moving.

"In a medium-sized tumour there could be a billion cells - and only a small proportion might break away and spread. So it is like trying to find, and understand, a moving needle in a very big haystack," says Sahai.

Sahai and his team used two groups of fluorescently labelled breast cancer cells inside live mice and tracked them with a technique called multiphoton confocal microscopy.

When the TGF-beta signal was blocked, the tumour spread via clumps of cells in the lymphatic system - limiting how far it could go, the researchers write.

But cells that could receive the TGF-beta signal moved as single entities, and the TGF-beta signal was first turned on - allowing the cells to spread through the blood, and then turned off - allowing them to grow again in a new location.

"It seems they can't multitask," says Sahai. "They can't move and grow at the same time, they can only do one or the other."

He says several pharmaceutical firms were investigating how to stop TGF-beta from functioning, but stressed they were "very much in the development phase".

"As yet there is no new drug in the pipeline," says Sahai, "But because we now know what these cancer cells are actually doing, it gives us lots of new ideas about how to stop them."

Tags: breast-cancer, cancer, genetics