Cancer: Research on mice shows chemical signalsmay determine where secondary tumours will strike
Researchers in the United States claim to have identified the process by which primary tumours determine the progression of secondary cancers in the human body.
The team from Cornell University in New York were investigating 'pre-metastasis', the developmental stage of metastatic or secondary cancer, which establishes where and why a secondary tumour will form.
They discovered that tumours release chemical signals that instruct bone marrow cells to embed themselves elsewhere in the body.
Once rooted into organ tissue, the bone marrow triggers the production of a protein, fibronectin, which creates a fertile environment in which a secondary tumour can grow.
As part of the same trial, the scientists also found that antibodies can be used to prevent bone marrow cells from spreading, thereby stopping their implantation in a secondary location and the development of another tumour.
The research was conducted on mice which were irradiated to kill all their bone marrow cells. These were replaced with fluorescent green bone marrow cells.
The rodents were then injected with skin and lung cancer cells tagged with red florescent protein.
Florescence was used to make it easier for researchers to trace cell movement at a microscopic level.
The researchers expected a primary tumour to develop in the skin and spread to the lungs, which it did.
Unexpectedly, however, they found that the bone marrow cells embedded themselves in the lungs several days before the cancer cells arrived. When they did, they took root in the same places as the bone marrow.
The experimenters then injected the solution in which the cancer cells had been cultured into the mice and found that this also directed bone marrow cells to the lungs, indicating that cancer cells secrete a substance that controls bone marrow movement, even outside the body.
The researchers have shown that antibodies can be used to block the migration of bone marrow cells and so could be employed in preventing the development of secondary cancers in humans.
The team also found intriguing evidence of 'pre-metastatic hot-spots' in the body.
These are receptive to the development of secondary tumours and may be determined by the genetic make-up of individual patients.
"This may explain why subsets of patients with early-stage colon cancer are more prone to liver metastasis, while others with an identical stage of cancer are cured of their disease with timely chemotherapy or surgery," said Dr Shahin Rafii, professor in genetic medicine at Cornell University.
"This is just the beginning. Preventing primary cancers from getting a toehold elsewhere in the body could be just the weapon patients need to prevent and fight metastatic disease," said Dr David Lyden, professor of cell and developmental biology at Cornell Medical College.
Clinical trials on patients are expected to begin by the end of 2006.
