Chemical Key to Cancer Spread
Mouse Studies Implicate Inflammation in Prostate, Breast Cancer
March 19, 2007 -- Immune responses inadvertently break down a barrier that
lets prostate cancer -- and maybe breast cancer -- spread throughout the body,
a new study suggests.
One of the body's most basic defenses is inflammation. Inflamed tissues
redden and swell with fluid. They give off a huge number of chemical signals to
attract attention from the rest of the immune system.
Cancers don't always cause inflammation. But inflammation is known to help
tumor cells grow. Now researchers at the University of California, San Diego,
have figured out one reason why.
Michael Karin, PhD, and colleagues suspected that a chemical signal, called
IKK-alpha, plays a role in prostate cancer. IKK-alpha signals breast tissue to
grow during pregnancy and seems to play a role in breast cancer.
In mouse studies, Karin's team found that IKK-alpha is indeed involved in
prostate cancer -- but in an unexpected way. The signal, they discovered, turns
off a gene that makes a protein called maspin. Maspin keeps tumor cells from
spreading through the body, a process called metastasis.
As long as prostate-cancer cells keep making maspin, Karin and colleagues
found, the cancer did not spread. But once they stopped making maspin, the
tumors spread like wildfire.
A little over a decade ago, Ruth Sager, PhD, and colleagues Dana-Farber
Cancer Institute discovered maspin -- and found that it prevents the spread of
"This confirms our suspicion there is something common to breast and
prostate cancers," Karin tells WebMD. "That is why we believe that what
we found for prostate cancer is likely to be relevant also for breast
Inflammation vs. Maspin
What makes tumor cells stop making maspin and start spreading through the
body? Karin's team turned up evidence that when inflammatory immune cells
invade tumor cells, they trigger IKK-alpha. And that, in turn, turns off maspin
More work is needed, Karin cautions. But all kinds of things -- including
tumor biopsy -- can cause inflammation.
"Anything that promotes inflammation may trigger this process
earlier," Karin says. "Injury [or] infection can certainly accelerate
this. And biopsy is not a neutral procedure, it is an invasive procedure ...
and they do it repetitively to follow the progression of the cancer.”
The good news, Karin says, is that the new findings will speed research into
new cancer drugs that would mimic maspin and prevent cancer spread.
Karin and colleagues report their findings in the journal Nature.