Yan Cui, PhD, Associate Professor of Microbiology, Immunology, & Parasitology at LSU Health Sciences Center New Orleans and the LSUHSC Stanley S. Scott Cancer Center, has been awarded a $1.5 million grant over five years by the National Cancer Institute to study the role of chronic inflammation in the development and progression of cancer.
Tumor suppressor protein 53, or p53, is a crucial molecule that is known to prevent cancer by either directly killing cancer cells or by stopping cancer cells from multiplying. The loss of p53 function resulting from genetic changes is detected in 50% of tumors and is considered to be one of the leading causes of cancer. However, p53 dysfunction caused by these mutations can also occur in normal cells surrounding the cancer cells, called stromal cells, and mutations in the p53 gene in some of them are associated with increased cancer spread and poor prognosis. According to the National Cancer Institute, a stromal cell is a type of cell that makes up certain types of connective tissue (supporting tissue that surrounds other tissues and organs). When cells become malignant, the surrounding stromal cells also change. So far, it is not entirely clear how these adjacent, normal cells that lack functional p53 affect the growth and replication of cancer cells.
This grant award is based upon published studies performed in Dr. Cui's laboratory, one of which was chronicled as a cover story in the March 15, 2013, issue of Cancer Research.
These studies demonstrated that a lack of functional p53 in tumor-associated stromal cells, as well as some of the immune cells, leads to an inflammatory microenvironment that suppresses the body's immune system to fight the cancer, increases the number of stromal cells infiltrating the tumor, and promotes blood vessel formation to nourish the tumor leading to its accelerated growth.
"These earlier findings broaden our understanding of the importance of this critical tumor suppressor protein as a guardian and gatekeeper for the proper function of patients' immune systems," notes Dr. Cui. "This newly funded project will further investigate whether hindering p53 causes chronic inflammation that creates an environment conducive for cancer formation, growth, and metastasis."
Dr. Cui will collaborate with Augusto Ochoa, MD, Director of the LSUHSC Stanley S. Scott Cancer Center, and Paulo Rodriguez, PhD, an assistant professor at LSU Health Sciences Center New Orleans, both leaders in the field of inflammatory cells and cancer. The long-term goal is to develop new approaches that target the p53 pathway and tumor-associated stromal cells to prevent or advance the treatment of cancer.
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