Inflammatory Protein MMP9 May Protect Against Bowel-disease-related Colorectal Cancer

Inflammatory Protein MMP9 May Protect Against Bowel-disease-related Colorectal Cancer

An inflammatory protein called MMP9 may protect against the development of a colorectal cancer associated with chronic inflammatory processes, such as inflammatory bowel disease (IBD), according to a study.

The research, “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.

Inflammatory processes protect the body against disease-causing pathogens or tissue damage. But when these processes become too active or unregulated, they can lead to several health conditions, such as cancer.

IBD, including ulcerative colitis and Crohn’s disease, is characterized by partial or total inflammation of the digestive tract. Those with the disease are at high risk of developing a colitis-associated cancer (CAC). The risk increases with inflammation duration and severity.

MMPs are a group of proteins that work by cleaving to other proteins, regulating their activity and maintaining cell function, both inside and outside the cell.

But when MMPs are too active or are at higher than normal levels, they can cause cell dysfunction, leading to several undesired consequences. Higher levels of certain MMPs help cancer cells grow and spread to other organs, for example.

MMP9 levels may actually protect against cancer, however. While normal cells have very low amounts of MMP9, inflammation prompts the epithelial cells lining the colon and intestine to produce the protein.

Researchers observed that mice with more MMP9 had fewer tumors and a higher rate of death of cells that were no longer needed, protecting against the development of cancer. Using human colon carcinoma cells with enhanced levels of MMP9, they also observed that there was less cell division and proliferation and less DNA damage, decreasing the risk of CAC.

Other experiments showed that MMP9 protects against cancer development by promoting the activation of a signaling pathway — MMP9-Notch1-ARF-p53 — that results in increased cell death, reduced cell division and better protection against DNA damage.

Together, the results support the idea that increased levels of MMP9 may defend the gastrointestinal tract against CAC by disrupting 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 news release.