Inflammation Key to Cancer Growth
It took 12 years and a creation of a highly sophisticated transgenic
mouse, but researchers at Kimmel Cancer Center at Jefferson have finally
proven a long suspected theory: Inflammation in the breast is key
to the development and progression of breast cancer.
December 15, 2010, issue of Cancer Research, the scientists
say they can now definitively show that an inflammatory process
within the breast itself promotes growth of breast cancer stem
cells responsible for tumor development.
also demonstrate that inactivating this inflammation selectively within
the breast reduced activity of these stem cells, and stopped breast
cancer from forming.
studies show for the first time that inactivating the NFKB inflammatory
pathway in the breast epithelium blocks the onset and progression
of breast cancer in living animals," says Richard G. Pestell,
M.D., Ph.D., Director, Kimmel Cancer Center and Chairman of Cancer
finding has clinical implications," says co-author Michael Lisanti,
Leader of the Program in Molecular Biology and Genetics of Cancer
at Jefferson. "Suppressing the whole body's inflammatory process
has side effects. These studies provide the rationale for more selective
anti-inflammatory therapy directed just to the breast."
and his colleagues show the "canonical" NFKB pathway promotes
breast cancer development: the first "insult" is provided
by the HER2 oncogene, which then activates NFKB (nuclear factor kappa-light-chain-enhancer
of activated B cells). NFKB turns on inflammation via tumor-associated
macrophages (TAM), which produce tumor growth promoting factors.
inflammation, mediated by NFKB, has long been thought to be important
in breast cancer development, the theory had been untestable because
NF-?B is essential to embryonic development, Dr. Pestell says. "When
you try to knock out NFKB genes in mice, they die."
this problem by creating a mouse in which the inflammatory system
within the adult animal's normal breast could be regulated. This allows
selective inactivation of NFKB in different cell types and took 12
years to accomplish, Dr. Pestell says. "These mice have five
are programmed to develop breast cancer, but the researchers found
that if they selectively blocked inflammation just in the breast,
tumors would not develop. "This is a very novel finding,"
Dr. Pestell says.
then demonstrated that this inactivation also reduced the number of
cancer stem cells in the breast. "That told us that inflammation,
through the action of NF-?B, is important to the growth and activity
of cancer stem cells," Dr. Pestell says. "The transgenic
mice are a new technology that can be used by the scientists and the
pharmaceutical industry to understand the role of NFKB in different
diseases including heart disease, neurodegeneration and other cancers."
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