Lactate Plays a Role in Development of Both Tumor Cell and Connective Tissue in Breast Cancer
New Brunswick, N.J.– Does lactate play a role in the metabolic fate of cancer cells? Researchers from The Cancer Institute of New Jersey (CINJ) are in Washington, D.C., this week for the 101st Annual Meeting of the American Association for Cancer Research (AACR) to share their findings on what role this common energy byproduct in the body plays in the development of breast cancer cells and surrounding connective tissue. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.
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.
Debabrata Banerjee, PhD, a scientist at CINJ and associate professor of medicine at UMDNJ-Robert Wood Johnson Medical School, is the senior investigator. “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,” he said.
The author team also includes Yanique I. Rattigan, PhD, UMDNJ-Robert Wood Johnson Medical School; Brij B. Patel, UMDNJ-Graduate School of Biomedical Sciences at Robert Wood Johnson Medical School and Rutgers, The State University of New Jersey; Pravin J. Mishra, MS, CINJ; Alister F. Martin, Rutgers University; and John Glod, MD, PhD, CINJ.
The study was supported by funding from the New Jersey Commission on Science and Technology, the New Jersey Commission on Cancer Research, and a T32 training grant from the National Cancer Institute (T32CA108455, Rattigan).
The work represented by CINJ members is among the 6,300 abstracts being presented at the gathering, which is featuring more than 17,000 researchers, healthcare professionals, and patient advocates. The event is open to registered participants.
About The Cancer Institute of New Jersey
The Cancer Institute of New Jersey (www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center dedicated to improving the detection, treatment and care of patients with cancer, and serving as an education resource for cancer prevention. CINJ’s physician-scientists engage in translational research, transforming their laboratory discoveries into clinical practice, quite literally bringing research to life. To make a tax-deductible gift to support CINJ, call 732-235-8614 or visit www.cinjfoundation.org. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.
The CINJ Network is comprised of hospitals throughout the state and provides a mechanism to rapidly disseminate important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. Major Clinical Research Affiliate Hospitals: Carol G. Simon Cancer Center at Morristown Memorial Hospital, Carol G. Simon Cancer Center at Overlook Hospital, Cooper University Hospital and Jersey Shore University Medical Center. Affiliate Hospitals: Bayshore Community Hospital, CentraState Healthcare System, JFK Medical Center, Mountainside Hospital, Raritan Bay Medical Center, Robert Wood Johnson University Hospital at Hamilton (CINJ at Hamilton), Saint Peter’s University Hospital, Somerset Medical Center, Southern Ocean County Hospital, The University Hospital/UMDNJ-New Jersey Medical School*, and University Medical Center at Princeton. *Academic Affiliate