Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts.

Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts.
Cell Mol Life Sci. 2019 Jul 03;:
Authors: Zhang Z, Gao Z, Rajthala S, Sapkota D, Dongre H, Parajuli H, Suliman S, Das R, Li L, Bindoff LA, Costea DE, Liang X
Abstract
Cancers show a metabolic shift towards aerobic glycolysis. By "corrupting" their microenvironment, carcinoma cells are able to obtain energy substrates to "fuel" their mitochondrial metabolism and cell growth in an autophagy-associated, paracrine manner. However, the metabolic changes and role of normal fibroblasts in this process remain unclear. We devised a novel, indirect co-culture system to elucidate the mechanisms of metabolic coupling between stromal cells and oral squamous cell carcinoma (OSCC) cells. Here, we showed that normal oral fibroblasts (NOFs) and OSCC become metabolically coupled through several processes before acquiring an activated phenotype and without inducing senescence. We observed, for the first time, that NOFs export mitochondria towards OSCCs through both direct contact and via indirect mechanisms. NOFs are activated and are able to acquire a cancer-associated fibroblasts metabolic phenotype when co-cultivation with OSSC cells, by undergoing aerobic glycolysis, secreting more reactive oxygen species (ROS), high L-lactate and overexpressing lactat...

Source: Cellular and Molecular Life Sciences : CMLS - July 2, 2019 Category: Cytology Authors: Zhang Z, Gao Z, Rajthala S, Sapkota D, Dongre H, Parajuli H, Suliman S, Das R, Li L, Bindoff LA, Costea DE, Liang X Tags: Cell Mol Life Sci Source Type: research