Inflammation of the breast and breast cancer
It has taken 12 years and the creation of a highly sophisticated transgenic mouse, but researchers at the "Kimmel Cancer Center" at Jefferson Medical University, have finally proven a long debated theory, namely:
Inflammation in the breast is key to understanding how breast cancer development and progression is triggered.
In "Cancer Research," scientists say they can now definitively show that an inflammatory process in the breast promotes the growth of breast cancer stem cells that are responsible for tumor development. They can also prove that selectively inhibiting this inflammatory response in the breast limits activity of these stem cells, and prevents the development of breast cancer. "These studies demonstrate for the first time that inhibiting the NFkB inflammatory process in the breast epithelium stops the onset and progression of breast cancer in living animals," said Richard G. Pestell, MD, Ph.D., director of the Kimmel Cancer Center and chair of Cancer Biology.
"This finding has clinical implications," said co-author Michael Lisanti, leader of the Program in Molecular Biology and Genetics of Cancer at Jefferson. "Suppressing inflammatory processes throughout the body comes with side effects. These studies provide fundamental rationale for selective anti-inflammatory therapy that targets the breast only. " Dr Pestell and his colleagues show that the "canonical" NFkB pathway promotes breast cancer development: the initial "damage" is delivered by theHER2 oncogene, which then activates NFkB ("nuclear factor kappa -light-chain-enhancer of activated B cells"). NFkB then initiates inflammation via tumor-associated macrophages (TAM), which produce tumor-growth promoting factors.
"Although inflammation, which is mediated by NFkB, has long been thought to play an important role in breast cancer development. Until now, this theory was not testable, because NFkB is essential for embryonic development," says Dr. Pestell. "If you try to turn off the NfkB genes in mice, they die." He then solved this problem by creating a mouse whose inflammatory response system could be regulated within the breast of an adult. This allows selective silencing of NFkB in different cell types and took 12 years to achieve. Dr Pestell said. "These mice have five co-integrated transgenes." The mice are programmed to develop breast cancer, but the researchers found that if they selectively inhibited inflammation only in the breast, tumors did not develop. "This is a very novel finding," says Dr. Pestell . They then showed that this elimination also reduced the number of cancer stem cells in the breast. " That told us that inflammation, through the action of NFkB, is important for the growth and activity of cancer stem cells," says Dr. Pestell. " The transgenic mice provide a new technology by which scientists and the pharmaceutical industry can learn to understand the role of NFkB in various diseases, including heart disease, dementia and other cancers."
The Canonical NF-κB Pathway Governs Mammary Tumorigenesis in Transgenic Mice and Tumor Stem Cell Expansion Cancer Research, Dec 15, 2010, by Liu M, Pestell RG, et al.
Source: Thomas Jefferson University (Philadelphia) press release, Dec 15, 2010
