Marcatori molecolari di cellule staminali nella cancerogenesi epatica sperimentale

Aim:Evolving under standing on tumor biology has led to the hypothesis that tumors may possess a stem cell–like subpopulation known as Cancer Stem Cells (CSCs) that may be involved in driving tumor pathogenesis and propagation.CSCs as well as normal tissue stem cells possess: self-renewal,unlimited proliferative capacity and pluripotency to differentiate in several cellular types. The aim of our investigation is to identify CSCs molecular markers,both prognostic and diagnostic value,that are associated with tumor initiation, heterogeneity, progression, metastasis, therapy sensitivity usefull potential for innovative therapeutic approaches.Methods:To this purpose we used two rats strains: F344 and BN,susceptible and resistant to chemically induced hepatocarcinogenesis respectively. We induced neoplastic liver lesions accordingly the resistant hepatocyte model. We evaluated,by immunoistochemical staining, CD44 (marker of oval cells and CSCs), CD133 (hematopoietic stem and progenitor cell marker), CK19 (marker of biliary cells and cholangiocytes) and c-Kit (markers of oval cells, CSCs and hepatocytes). Sections were obtained from untreated controls and tumor tissue.Results:Our immunoistochemical observations showed significant differences of basal levels (controls) between the two rat strains, susceptible and resistant, as concernes CK19 (p=0.03);CD133 (p=0.0003) and c-Kit (p=0.0003) expression,but CD44. In BN rats,resistant strain,all 4 markers showed higher levels in tumors compared to their controls (p=0.0001). In F344 rats,susceptible strain, 3 markers showed higher levels in tumors (between 2 and 3 folds) compared to controls, except CK19. Only CD133 and CK19 are significantly higher in HCC from BN rats compared to tumors from F344. Unfortunately at the moment we were able to analyse only few numbers of rats.Conclusion:Based on these data, we may suggest that the stemness markers studied could represent valuable diagnostic and prognostic markers for hepatocellular carcinoma, since stem cells can contribute to tumor progression, as it has already been shown in other several types of tumors.