Molecule linked to lung cancer growth and spread
Tuesday 24 April 2012
MMP-10 is required for the growth of 'stem cells' in non-small cell lung cancer, say scientists at the Mayo Clinic in Florida.
Cancer stem cells are thought to be behind the growth of many cancers, and are often resistant to radiotherapy and chemotherapy.
Shutting down MMP-10 stopped signs of stem cell activity and blocked tumour growth in mice.
MMP-10 also helped tumours to spread, or metastasise.
The findings, published in the journal PLoS ONE, suggest that MMP-10 may also be crucial to the survival of other types of cancer.
Dr Alan Fields, from the Mayo Clinic's department of cancer biology, said that MMP-10 plays a "dual role" in cancer - stimulating both the growth of cancer stem cells and their ability to spread.
He added: "This helps explain an observation that has been seen in cancer stem cells from many tumour types, namely that cancer stem cells appear to be not only the cells that initiate tumours, but also the cells that give rise to metastases."
Dr Fields said the discovery that lung cancer stem cells express MMP-10 and use it for their own growth was unexpected, because most known metalloproteinase genes are expressed in the cells and tissue surrounding a tumour - the tumour's so-called microenvironment.
The findings also show that cancer stem cells produce much more MMP-10 than other tumour cells.
Dr Fields said: "MMP-10 acts to keep these cancer stem cells healthy and self-renewing, which also helps explain why these cells escape conventional chemotherapy that might destroy the rest of the tumour.
These findings indicate that high levels of MMP-10 may also play a crucial role in the survival of other cancer stem cells.
A similar link appeared between MMP-10 and the metastatic behaviour and stem-cell like properties of bowel cancer, melanoma, breast, renal, and prostate cancers.
Dr Gillian Murphy from Cancer Research UK's Cambridge Research Institute said it was "unusual and interesting" that MMP-10 might have a role in maintaining tumour stem cells in lung cancer, rather than just the cells surrounding the cancer.
She added: "The MMP enzymes are involved in many processes in the body, and lots of work has already shown they have many roles in cancer. But this is the first indication that they don't just control processes in the tissues surrounding a tumour, but actually might control cancer cell behaviour. It will be exciting to learn exactly what MMP-10 is doing, as this work only shows the enzyme could be involved in regulating cancer cells, not how it's involved.
"MMP-10 also has a major role in wound healing, and perhaps there's a link between how it helps the body repair injury and how it's involved in cancer."
She said that a "big hurdle" to moving this work from the lab into patients will be the challenge of designing a drug that blocks MMP-10. The molecule has a lot of close 'cousins' structurally and "it has been very hard to design specific chemical inhibitors so far".
Copyright Press Association 2012
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