‘Jekyll and Hyde’ molecule may help pave the way to personalised medicine for prostate cancer patients
Researchers at the University of Hull have uncovered the harmful, hidden nature of a molecule involved in prostate cancer.
In a series of two recently published papers*, researchers at the University of Hull have shown that prostate cancer patients who have a molecule called Endo180 present in their tumours tend to have more severe disease.
Around 65 per cent of men with Endo180-positive tumours died within five years of diagnosis, compared to just 39 per cent who did not have Endo180. These results suggest that Endo180 contributes to thousands of prostate cancer deaths. And the team have also uncovered why this might be.
When cancer enters its advanced stages, cells from the tumour can escape into the bloodstream and travel around the body. Some of these cells can then colonise bones and other organs, leading to the growth of secondary tumours, and nearly all cancer-related deaths are the result of this process.
This new research suggests that Endo180 is critically involved in the progression of prostate cancer in this way, as Dr Justin Sturge, lead researcher and Senior Lecturer in Biomedical Science at the University of Hull explains:
“It’s a real Jekyll and Hyde scenario,” he said. “We found that in healthy ‘non-cancerous’ prostate cells Endo180 is normally stuck to another molecule, and this pairing completely suppresses the cells from behaving dangerously. However, when we broke the two molecules apart, Endo180 completely flipped its role and actively encouraged cells to break away from each other, which is the deadly feature of those cancers that start to spread to other parts of the body.”
Interestingly, further work by the team has also found that physical changes in prostate tissue that occur during normal ageing can trigger this sudden switch in Endo180 activity.
“We’ve not only shown that Endo180 is a strong predictive marker of disease severity in patients with prostate cancer, but we’ve also uncovered a potential new way to monitor and target the disease” says Dr Sturge.
“We believe this research will ultimately help pave the way to more personalised medicine for prostate cancer patients. Our findings suggest that if a patient has early disease that is positive for Endo180, we can help limit their disease by stabilising the protein before it ‘turns’. The next stage is developing new treatments that can do this.”
Dr Helen Rippon, Head of Research at Worldwide Cancer Research who helped fund this work said:
“Personalised medicine is a really exciting area of cancer research right now and Dr Sturge’s work shows just why that is – the potential benefits are huge. If we can target the right treatment to the right patient at the right time, then not only can we improve cancer survival, we can also reduce unnecessary treatments and side-effects for those who don’t need it.”
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Domain Interaction of Endo180 and CD147 Survival outcome and EMT suppression mediated by a lectin domain interaction of Endo180 and CD147. M. Rodriguez-Teja, JH. Gronau, A. Minamidate, S. Darby, L. Gaughan, C. Robson, F. Mauri, J. Waxman, and J. Sturge. Mol Cancer Res; 2014; doi:10.1158/1541-7786.MCR-14-0344-T
AGE modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival. M. Rodriguez-Teja, JH. Gronau, C. Breit, Y. Zhi Zhang, A. Minamidate, MP. Caley, A. McCarthy, TR. Cox, JT. Erler, L. Gaughan, S. Darby, C. Robson, F. Mauri, J. Waxman and J. Sturge. Journal of Pathology. DOI: 10.1002/path.4485