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Chemical signals 'spread cancer'

Tumours send out chemical signals
US scientists say they have discovered how tumours control the development of secondary cancers in the body.
Writing in Nature, they say primary tumours emit chemical signals.

These make the target sites for secondary tumours sticky and direct bone marrow cells to them to secure a foothold for arriving tumour cells.

New York's Cornell University used antibodies to block bone marrow cells' migration in mice, and believe their work could help humans.


For the first time we have shown the initial steps involved in metastasis
Dr David Lyden

Initially, growth factors released by the primary tumour trigger the production of an adhesive protein called fibronectin on the surface of cells at the target site.

Then a second tranche of growth factors is released to encourage bone marrow cells to zero-in on the same site.

Once there, they cluster in groups, forming a support structure which stabilises the malignant cells that arrive later to begin forming a secondary, or metastatic, tumour.

The researchers have shown that it is possible to block the migration of bone marrow cells by using antibodies.

In theory the technique could be used on cancer patients to block the latter stages of their disease.

Fluorescent markers

The experiments were carried out on mice that had been irradiated to kill off all their bone marrow cells.

These were then replaced by bone marrow cells tagged with a green fluorescent protein, which enabled their movement to be easily traced under a microscope.

Once the new bone marrow cells were established, the mice were injected with lung or skin cancer cells, each marked with a red fluorescent protein, again to make them easy to follow.

The tumour cells were expected to form a primary tumour in the skin, and then to spread to the lungs.

The researchers found that the green bone marrow cells appeared in the lungs days before any of the tumour cells reached the same site.

Eventually the tumour cells did turn up - in exactly the same locations as the bone marrow cells.

The researchers then injected the mice with the medium in which the cancer cells had been cultured, rather than the cells themselves.

This also caused the bone marrow cells to move to the animals' lungs, implying the cancer cells had secreted some factor into the surrounding solution that controlled bone marrow cell movement.

Lead researcher Dr David Lyden told the BBC News website: "For the first time we have shown the initial steps involved in metastasis.

"By blocking bone marrow cells using antibodies, we are capable of preventing tumour cells implanting and thus the spread of cancer."

Dr Lyden said it was hoped to start clinical trials on patients within a year.

Dr Julie Sharp, of the charity Cancer Research UK, said: "This research provides a fascinating new insight into how tumour cells spread around the body.

"The study was carried out in mice, but assuming this mechanism is the same in humans, this process could be targeted with specific anti-cancer drugs in the future, helping to prevent cancer spread."