Authors: Libby Brooks
Mentors: Natasha Pavlova
Insitution: University of Utah
About 90% of cancer deaths are from the development of secondary tumor growths from a process called metastasis. As cancer cells divide uncontrollably nutrients from nearby tissue – specifically the amino acid glutamine – are depleted. Glutamine is one of the most abundant amino acids in the bloodstream, and most cells cannot live without it. Tumors have poor vasculature which further contributes to the depletion of nutrients. Even in nutrient-depleted environments, tumors have found ways to grow.
Tumors are comprised of cancer cells as well as non-cancerous stromal cells. Studies have shown stromal cells can synthesize glutamine which they release into the tumor microenvironment feeding cancer cells and allowing them to grow. However, the signaling pathway used between the cancer and stromal cells in this relationship remains unclear.
To study the signaling pathway by which stromal cells are synthesizing glutamine I treated cells with a common anti-inflammatory drug, dexamethasone. Mice receiving dexamethasone over a long period of time had increased lung metastases when injected with cancer cells. Dexamethasone binds to the glucocorticoid receptor (GR) which activates the expression of glutamine synthetase (GLUL) enzyme mRNA. The expression of GLUL causes the cell to synthesize glutamine. However, the role of GR, in regulating GLUL expression in tumors, remains insufficiently studied.
The experiments done for this project show that dexamethasone induces GLUL expression in stromal cells such that they start releasing glutamine. This may promote growth of cancer cells even when there is a deficit of nutrients around. It is hypothesized that due to this property, dexamethasone increases risk of metastasis. This project will aid in the development of cancer therapeutics to treat metastatic cancers.