Elucidating the Effects of Prolonged Leukocytic and Metastatic Cell Exposure to P-selectin and ICAM-1 on Cell Activation and Survival

Abstract

The immune system has been well studied for its importance in protection against pathogens and healing of inflamed human tissues. It is known to intervene in chronic inflammation of diseases including cancer. Although much attention has been given to its role in protection against diseases, emerging research show that the immune system contributes to the development of some cancers like the colon carcinoma. The purpose of this research is to analyze what signaling mechanism cancer uses to manipulate the immune system to survive and metastasize. The study looks at the first process of immune intervention by analyzing the process of monocyte recruitment. Cell adhesion molecules located in the endothelium initiate the rolling and firm adhesion of monocytes, P-selectin and ICAM-1 respectively, near the location of inflammation. Apoptosis, a voluntary cell death, is a mechanism this research analyzes for monocyte activation after interacting with cell adhesion molecules. Recent work from our lab has shown that monocytes have more interaction with P-selectin than colon carcinoma, indicating a potential critical point of avoiding being attacked by the immune system. Results in this study show that P-selectin increases the number of Phosphatidylserine (PS) in formation of apoptosis in both monocytic THP1 cells and colon carcinoma LS174 T cells. In addition, current study shows that co-incubation of P-selectin with intracellular adhesion molecule-1(ICAM-1) decreases the number of PS exposure. These results might be crucial in understanding the underlying mechanisms in which cancer cells survive and thus, suggesting that developing therapeutic drugs that target ICAM-1 might be a possible route in decreasing cancer’s ability to metastasize.