Scientists in the US have discovered that cancer tumors that don’t spread to other parts of the body secrete a protein called prosaposin and that metastatic tumors, which do spread, don’t secrete much of it. They suggest this discovery could lead the way to developing new treatments that stop cancers from spreading.
The research was the work of a team at Children’s Hospital Boston, Massachusetts, led by Dr Randoph S. Watnick, an assistant professor in the Vascular Biology Program at the hospital. The findings are about to be published in the Proceedings of the National Academy of Sciences.
Metastasis, where cancer spreads from the original site to other parts of the body, is one of the main causes of death from cancer, so a treatment that stops it would make a huge difference to survival. Currently there are no approved treatments that work on this basis.
Watnick and colleagues had already discovered that metastatic tumors don’t just start spreading to other organs: they prepare their “landing places” by secreting proteins that encourage tumor cells to grow in the new site by doing things like attracting feeder blood vessels so when the migrating tumor cells get there they hit the ground running.
Now, in this latest study, they report finding a protein called prosaposin that stops the advanced site preparation by producing compounds that block the growth of blood vessels. They found that tumors that don’t become metastatic, that is they stay local, secrete prosaposin.
They looked at cells from localized prostate and breast tumors that didn’t metastasize, and found they secreted high levels of prosaposin, whereas cells from tumors that had spread secreted very little of it.
They investigated the effect of the protein further by doing tests in live mice. They injected the mice with tumor cells that they knew from previous research would spread to other organs, but this time they also added prosaposin to the cells.
The result showed that lung tumors from metastasis were reduced by 80 per cent, lymph node metastases were completely eliminated (when cancer spreads it uses the lymph nodes as transport channels), and the mice lived significantly longer.
And when they suppressed the prosaposin in the tumor cells, the metastases increased.
Also, when the researchers injected the prosaposin directly into the mice rather than inserting it into the tumor cells first, they found the tumor cells formed hardly any metastases colonies in the lungs, and when they did, the colonies were much smaller. And the mice lived 30 per cent longer than mice that did not receive prosaposin.
Looking at the underpinning mechanisms, the researchers found that prosaposin stimulates a well known tumor suppressor called p53 present in the tissue around the tumor. This switches on production of the natural angiogenesis inhibitor thrombospondin-1 that stops blood vessels being made in the local and the remote tumor sites.
Watnick told the press that:
“Prosaposin, or derivatives that stimulate p53 activity in a similar manner in the tumor stroma, might be an effective way to inhibit the metastatic process in humans.”
If this effect can be replicated in humans, Watnick suggests there will come a day when cancer patients are treated for their primary tumor and at the same time are given drugs that stop or slow any chances of it spreading.
“While we may not be able to keep patients from getting cancer, we can potentially keep them metastasis-free,” he added.
Dr Julie Sharp, senior science information manager at Cancer Research UK was equally hopeful:
“While this research is in its early stages it could help researchers to develop drugs that stop or slow down cancer spread,” she said.
Sources: Children’s Hospital Boston, Cancer Research UK.
Written by: Catharine Paddock, PhD