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Protein that helps skin cancer spread identified by Stanford researchers

on in the children's collagen VII gene. The cancer-resistant skin cells were from children who lacked the collagen VII protein altogether. The remaining cancer-prone samples all contained just a fragment of the protein. Both types of mutations leave the children equally prone to RDEB, but only those cells that contained a portion of the collagen VII protein were susceptible to cancer.

Khavari and his group deduced that this collagen VII protein fragment might be necessary to allow cancer to form. They proved this by adding the fragment to RDEB cells that lacked it-an intervention that restored cancer-forming ability.

Further proof came from work in normal skin cells. The group blocked that protein fragment using an antibody and once again tried to induce the cells to become cancerous. They failed. Without that fragment, the cancer could not spread.

Khavari noted that cells behave differently when they are in a lab dish versus growing as part of an animal. With that in mind, he and his group transplanted some human skin cancer cells onto mice. As expected, those cells formed skin cancers that would kill the mouse if left unchecked.

But when the group treated the mice with the collagen VII-blocking antibody, the skin cancer failed to spread, though the cancer remained. "This cancer isn't deadly unless it spreads," Khavari said.

What's more, it appears that the antibody blocks only the cancer-spreading aspect of collagen VII. The protein is still able to perform its normal job of keeping the skin intact.

Khavari stressed that all this work took place using human cells. "Cancer processes are very different in humans and mice," Khavari said. If they'd found these results in mouse cells, the group would still need to prove that the fragment is relevant for humans. By studying human cells, the group has already shown the fragment's relevance-now it's just a matter of using that knowledge to treat patients.
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Contact: Amy Adams
amyadams@stanford.edu
650-723-3900
Stanford University Medical Center
17-Mar-2005


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