Clue hints at how breast cancer spreads

updated 5:34 p.m. ET Oct. 19, 2009

LONDON - Scientists who watched tumor cells spread in living mice said on Sunday they had found a gene signal controlling how cancer cells move, which could help companies design new drugs to fight the disease.

Scientists working for Cancer Research UK used hi-tech imaging techniques to watch how breast cancer cells spread in mice. They found that a genetic signal, known as TGF-beta, was crucial to whether cells moved as single entities or in clumps.

TGF-beta signaling 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," said Erik Sahai, head of the tumor cell biology lab at Cancer Research UK's London institute.

He said 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," said 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."

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 tumors 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 tumor 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," said Sahai.

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

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

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

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