By: Paul Browne

Paul Browne — Tue, 16 Jun 2009 12:56:40 +0000

This isn’t the only interesting cancer research news this week, the BBC reports that scientists from the University of Heidelberg have made an important discovery about the role played by signalling proteins granulocyte- and granulocyte-macrophage colony-stimulating
factors (G-CSF ans GM-CSF) in the often severe pain associated with many cancers. Cancer pain has long been known to be different to other kinds of pain, and is difficult to treat

http://news.bbc.co.uk/1/hi/health/8089306.stm

G-CSF and GM-CSF are known to play a role in the development of blood cells, but Dr. Matthias Schweizerhof and colleagues were surprised to find high levels of these proteins in the pancreas of pancreatic cancer patients, and that nerves in this tissue had the receptors that bind them.

To examine this further they used a mouse model of bone tumor–induced pain that closely mimics that seen in human patients, and again found high levels of G-CSF. GM-CSF and their receptors. In vitro studies on nerve tissue from mice showed that G-CSF and GM-CSF made nerves associated with pain (nociceptive nerves) more sensitive. They then found that mice whose paw was injected with G-CSF and GM-CSF withrdrew it more quickly from a painful mechanical or heat stimulus, indicating that they were more sensitive to pain and quickly took action to avoid it, and observed the same in mice with bone tumours.

Having demonstrated a role for G-CSF and GM-CSF in pain they sought to see whether they could block it, and did so by injecting antibodies against G-CSF and GM-CSF in the mouse bone tumour model. But these injections also slowed the growth of the tumours, something that had been observed before, so they wanted to make sure that the lower pain levels were not just due to the tumours being smaller. To do this they injected a viral vector into the nerves adjecent to the tumour that expressed short hairpin RNAs that block the production of the receptors for G-CSF and GM-CSF, which if their theory was correct would stop the signalling peptides from increasing sensitivity to pain. The pain levels were again reduced, even though tumour growth was unaffected, proving that G-CSF and GM-CSF directly increase sensitivity to pain.

This is a discovery that will hopefully allow us to treat cancer pain by local injection of drugs or antibodies that block G-CSF and GM-CSF, something that would help tens of thousands of cancer patients. It also provides an explanation of why some patients who are given GM-CSF and G-CSF to encourage blood cell growth after chemotherapy or before donating stem cells suffer serious bone pain, and may lead to the development of procedures and treatments that might reduce such painful side effects.

Schweizerhof M. et al. “Hematopoietic colony–stimulating factors mediate tumor-nerve interactions and bone cancer pain” Nat Med. published online June 7 2009 DOI:10.1038/nm.1976

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By: Paul Browne