Abstract B06: Impact of intratumoral microenvironment and epithelial cells crosstalk in pancreatic carcinogenesis

In this study, we used a laser microdissection approach of human PDAC stromal and epithelial compartment, followed by mass spectrometry and bioinformatics analysis (statistics/interactome) to compare protein composition and networks within both compartments. We found the presence of a proteic complex composed of three proteins, expressed only in stromal compartment, related to lipid and intracellular trafficking. To validate such data, we confirmed the specific stromal expression of each protein, on human PDAC samples, and found that our three targets were expressed mainly in stellate cells. However before to investigate the dialogue between epithelial and stromal cells, we designed an in vitro model, based on co-culture of stromal cells: immune and stellate cells, which take into account the multi-cellular composition of such tumors and added PDAC relevant metabolic stresses: hypoxia and nutrient starvation. To improve our model, we used primary stellate cells that we extracted from freshly resected human PDAC tumor pieces. We added pancreatic tumoral cells in our model to investigate dialogue between stromal and tumoral cells. Our data show that under nutrient and hypoxic stresses, co-cultures from stellate and immune cells provide a proliferative and pro-migratory advantage to tumor cells. Moreover, and only in these same specific condition, the proteic complex identified is formed in stellate cells. So, we hypothesized that a specific “lipid related process” is develo...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Inflammation/Stroma Source Type: research