An inflammatory protein called MMP9 may protect against the development of colitis-associated cancer (CAC), a type of colorectal cancer associated with chronic inflammatory diseases, a new study says.
The study, “Epithelial Derived-Matrix Metalloproteinase (MMP9) Exhibits A Novel Defensive Role Of Tumor Suppressor In Colitis Associated Cancer By Activating MMP9-Notch1-ARF-p53 Axis,” was published in the journal Oncotarget.
The immune system protects the body against pathogen invasion or tissue damage, but when inflammatory processes become too active or unregulated, they can result in the development of several health conditions, including cancer.
Chronic inflammatory diseases, such as ulcerative colitis and Crohn’s disease, are characterized by partial or total inflammation of the digestive tract, leaving patients at a significant high risk (as high as 50%) of developing CAC. This risk further increases when inflammation has a chronic and severe status.
Matrix-metalloproteinases (MMPs) are a group of proteins whose function is to remodel the extracellular matrix, regulating cell-cell interactions and the release of growth factors and cytokines that typify normal cell function. However, when these proteins become too active or are present in increased levels, they may dysregulate cell function and result in several undesired consequences. For instance, increased levels of certain MMPs help certain types of cancer grow and spread to other organs.
MMP9 levels, however, seems to protect against the development of CAC. Researchers found that normal cells have very low amounts of MMP9, but inflammation promotes the expression of this protein by the cells lining the surface of the colon and intestine (called epithelial cells).
They also found that mice expressing increased levels of MMP9 had fewer cancer incidences and presented increased levels of death among cells that no longer were needed, which decreased the risk of cancer.
Researchers also observed that human colon carcinoma cells with increased expression of MMP9 divided less often and presented less DNA damage, which decreases the risk of CAC. Additional experiments indicated that MMP9 protected against cancer development by activating a molecular pathway (MMP9-Notch1-ARF-p53) that increased cell death, reduced cell division, and controlled DNA damage.
These results suggest that increased levels of MMP9 may protect the gastrointestinal tract from CAC onset by disturbing several factors that would otherwise lead to the development of this type of cancer.
“In the setting of chronic inflammation, MMP9 expression functions as a silver lining by suppressing the advancement of the tumor microenvironment in CAC,” Pallavi Garg, senior author of the study, said in a press release.
