Congratulations to Mei Kong on her American Cancer Society Research Award for her proposal, “Dissecting the role of secreted metabolite in colon cancer metastasis”.
Award Summary: The major cause of death in most cancer patients is metastases. Metastasis occurs when cancer cells leave the primary site of occurrence and thrive in distant organs. Despite many breakthroughs that continue to improve the outcome for treating primary tumors, patients with metastatic cancer have very limited options for therapies. Thus, understanding the complex biology that takes place between the primary tumor and the time metastasis occurs will be critical to establish future therapies targeting late-stage metastatic cancer. As the primary tumor evolves, cancer cells leave the primary site and enter the blood stream. On the other side of the metastasis, the cell must find a place to hide from the immune system and adapt to new tumor microenvironments. Although much has been learned about the behavior of cells in the primary tumor, we are only now beginning to understand the complex biology of the cell after the cancer cell resides in their new tissues. One of the most important challenges for cancer cells to seed and grow in in a foreign tissue is the ability to adapt metabolically to a new nutrient landscape. However, how metastatic tumor manipulate the foreign metabolic microenvironment is not known. In preliminary studies, we investigated what metabolites are secreted from metastatic colon cancer and compared them to primary cancer. Surprisingly, we found that metastatic colon cancer cells specifically secrete a metabolite, named pyruvate, at a significantly higher rate than the primary tumor cells. Interestingly the metabolic rate of production of pyruvate remains the same between metastatic and primary cancer cells suggesting there is an active decision by the cell to expel it. We also found expression of a pyruvate transporter that release pyruvate to the outside of the cells is more abundant in metastatic cells in human cancers. This exploratory project will test a novel idea that cancer cell-secreted pyruvate plays a critical role to allow metastatic cells to seed in the foreign metabolic environment and inhibition of this transporter may lead to a new therapeutic potential to kill metastatic cancer cells.
