Inflammatory mediators & lung cancer progression
Initial Award Abstract
In the fight against lung cancer, encouraging people to quit smoking is very important, but unfortunately, risk of lung cancer does not vanish when someone quits. Risk of cancer development is highest in current smokers, lower in former smokers and lowest in never smokers. In the first decade after giving up smoking, the risk of lung cancer decreases by 50% over current smokers, yet there is still an increased lung cancer risk for former smokers over never smokers 30 years after quitting.
Due to constant exposure to tobacco smoke, smokers’ lungs display features of chronic inflammation. Inflammation is usually helpful; it’s part of a healthy body’s response to irritants, injury or illness. Chronic inflammation though, occurs when the body does not shut off its response to these events. During chronic inflammation, many different molecules are overexpressed including tumor necrosis factor-alpha, prostaglandin E2, transforming growth factor-beta and interleukin-1 beta (IL-1beta). This chronic inflammation is a risk factor for the development of lung cancer. However, how these inflammatory molecules affect cancer progression is not known. The focus of this research is on the role of IL-1 beta in inflammation-promoted lung cancer. Studies have shown that the expression of IL-1 beta is increased in a number of cancers, including lung cancer. In patients, the presence of IL-1 is associated with tumor aggressiveness and poor prognosis. We hypothesize that IL-1 beta promotes the progression of lung cancer by induction of epithelial-mesenchymal transition (EMT). EMT is a process whereby epithelial cells which should be stationary and attached to each other no longer make the proteins to allow them to do so. Instead they begin producing proteins normally made by cells that are mobile. Cell adhesion proteins such as E-cadherin show decreased expression while expression of proteins such as N-cadherin and vimentin are increased. When cancer cells lose the ability to attach to each other and gain the ability to move, this sets the stage for cancer to spread or metastasize. Metastasis refers to the spreading of cancer from the organ it began to grow in to other organs in the body.
Lung cancer is responsible for almost 30% of all cancer deaths with smokers and former smokers accounting for 80-90% of lung cancer cases. Only 15% of patients with lung cancer will survive 5 years after diagnosis. This is a figure that has changed little over the past 25 years and is largely attributed to the fact that lung cancer is most often not diagnosed until metastasis has occurred. In fact most cancer-related deaths are due to metastatic spread. Investigation of the factors involved in promoting metastasis is an important part of identifying new targets for therapies for lung cancer patients and lung cancer prevention. |