Robert Wood Johnson Medical School
Department of Pharmacology
The Cancer Institute of NJ
195 Little Albany Street
New Brunswick, NJ 08901
Breast cancer, wound healing, carcinoma associated fibroblasts, chemokines
Role of carcinoma associated fibroblasts in supporting tumor growth: Our recent studies indicate that bone marrow-derived mesenchymal stromal cells (MSCs) exposed to tumor-conditioned medium assume a CAF-like myofibroblastic phenotype and serve as an excellent in vitro model for understanding tumor stroma interactions. More importantly, these cells also exhibit functional properties of CAFs including increased expression of stromal derived factor 1 (SDF-1) and the ability to promote tumor cell growth both in vitro and in an in vivo coimplantation model. Further studies on tumor stroma interactions have revealed that metabolic support from stromal cells is critical for tumor cells to survive and proliferate at the metastatic site. We hypothesize that stromal cells are important for tumor metastasis as they provide critical metabolites via a lactate pyruvate shuttle ensuring tumor growth. Our investigations indicate that a lactate pyruvate shuttle exists between tumor and stromal cells where lactate produced by glycolytic tumor cells is taken up by stromal cells and converted to pyruvate which along with glutamate and gamma amino butyrate is returned to tumor cells as metabolites for continuation of glycolysis as well as for increasing biomass. Current work in the laboratory is focused on understanding and targeting this dialog between tumor cells and CAFs.