A PROTEIN found in the blood of cancer patients can behave just like a prion,
the infectious agent that causes mad cow disease. Its discoverers think it might
help cancers spread throughout the body.
鈥淲e always tend to think of cancer as a genetic disease, caused by
mutations,鈥� says Mike Scott, a prion researcher at the University of California,
San Francisco. 鈥淏ut there is this distinct possibility that there might be some
prion-like mechanism involved in at least some tumours.鈥�
This is the first example, he says, of a prion-like protein in mammals that
doesn鈥檛 belong to the family of proteins called PrP, which cause scrapie and BSE
as well as its human variant, vCJD. Prions are an abnormal form of PrP. They
persuade normal PrP proteins to turn into the rogue form, which can resist heat
and enzymes called proteases that normally break down proteins.
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It鈥檚 this ability to alter other proteins that James Morr茅 and his
colleagues at Purdue University in Indiana discovered in a cancer-related
protein called tNOX. Morr茅鈥檚 team digested proteins from human cancer
cells using an enzyme called proteinase K. Afterwards, they found another
protein survived as well as tNOX. 鈥淲e were not looking for it, but there it
was,鈥� says Morr茅.
It turned out to be a protein called GAPDH, which is normally digested by
proteinase K. Was tNOX making GAPDH resistant to the protease? To answer that,
Morr茅 and his team incubated tNOX and normal GAPDH together. In every
case GAPDH became protease-resistant, they report in a paper that will appear in
Biochemistry. The tNOX was acting like a prion.
And that was not the only similarity. The tNOX protein also forms insoluble
lumps, or plaques, and resembles the prion that causes scrapie. However, the
researchers don鈥檛 know how tNOX itself becomes like a prion.
But unlike known prions, which alter proteins similar to themselves, tNOX
modifies an entirely different protein. This is another first, Scott says.
鈥淓veryone expected this would happen sometime. But this is the first example
where a prion-like protein seems to be able to convert a different protein into
a prion-like form,鈥� he says.
In addition, tNOX can do its normal job while acting like a prion. 鈥淭his is
tremendously significant,鈥� says Scott. 鈥淭here鈥檚 an obvious selective advantage
in being converted into the prion-like state, because the protein has full
activity but is now resistant to proteases.鈥�
Morr茅 found the protein鈥檚 concentration was highest in the blood of
people whose cancers had spread through their body. He suspects the protein
might help cancers spread. 鈥淚 believe it does, but there鈥檚 no hard evidence to
support that,鈥� he says.
But he stresses that tNOX protein cannot 鈥渋nfect鈥� other people. He鈥檚 tried
injecting the protein into healthy mice. 鈥淭he mice do not get cancer. This would
be required if this were a real disease threat in terms of transmission,鈥� says
Morr茅. What is not clear is if the protein, when present, could tip the
balance in cells that are already becoming cancerous for other reasons.