Researchers from The Cancer Institute of New Jersey (CINJ) have revealed the role lactate plays in the development of breast cancer cells and surrounding connective tissue.
A known energy source for cancer cells is blood sugar (glucose), which helps convert food into a useable resource for the cell.
Cancer cells also can convert glucose into lactic acid (or lactate), which can result in excess accumulation of this chemical in the cell. In order for tumor cells to thrive, the lactate needs to be expelled from the cell.
This function is carried out by a family of proteins (monocarboxylate transporters) that transport this lactic acid across cell membranes.
Previous study shows that breast cancer development and disease spread are highly dependent on specialized connective tissue (stroma), particularly carcinoma associated fibroblasts (CAFs), as tumors rarely develop in the absence of this tissue.
CAFs are known to support tumor growth and may cause tumor cells to be drug resistant. The exact role of stroma in the development of breast cancer remains unclear and is an area of intense investigation.
To explore whether lactate produced by tumor cells is used as an energy source for stromal cells-in effect forming a small ecosystem where lactate is an essential element -- the team developed an experimental system to generate CAFs from bone marrow-derived mesenchymal stem cells (MSCs), which make up the outer connective tissue of a cancer tumor.
Investigators have demonstrated the ability of these CAFs to promote tumor growth both in laboratory and experimental models using a cell line that represents the basal subtype of human breast cancer.
They found that CAFs can remove lactate from the tumor environment and utilize it as an energy source by increased activity of monocarboxylate transporters.
In exchange, the CAFs support tumor growth by providing the tumor with the stimulation necessary to secrete proteins in order to regulate certain cellular functions. One of these functions is the recruitment of MSCs through cell migration, in essence, directing strategic placement of these cells.
"These studies will increase our understanding of metabolic cooperation between two of the principal players in the tumor environment and will yield information regarding important targets permitting future development of focused therapies for stroma reliant tumors," said Debabrata Banerjee, a scientist at CINJ and associate professor of medicine at UMDNJ-Robert Wood Johnson Medical School, is the senior investigator.
The findings have been presented this week at the 101st Annual Meeting of the American Association for Cancer Research (AACR).