Molecular evidences of the stem cells contribution during progression of pituitary adenoma development

ZLOCOWSKI N; GUTIERREZ S; TORRES A I; GUIDO C; PEREZ P; PETITI JP; SOSA L; MOYANO, G; MUKDSI J

La Falda Córdoba

Congreso; 5to Congreso Argentino de Microscopia; 2018

Our previous results confirmed the presence of stem cell (SC) in adult pituitary gland and provided early evidences of cells expressing cancer stem cells (CSC) markers in experimental pituitary adenomas. The aim of this study was to evaluate possible changes in the expression of CS: GFRa2, Oct-4, Sox2, Nestin, Progenitor (P): Sox9, and CSC: CD133 and CD44 markers, during experimental pituitary tumor development, and later characterization of the SC in culture. MyM:The experimental model in vivo was performed in female Fischer rats, treated with 30mg of estradiol benzoate during 5 (5D), 10 (10D), 20 (20D) and 30 (30D) days. Control group (C) included rats in diestrous. SC/P and CSC markers were detected by immunofluorescence (IF) and Western Blot (WB). In vitro studies were done using C, 5D and 30D pituitary cell suspensions. The 30D spheres were characterized by IF of SC/P and CSC markers and further estrogen stimulation and proliferation quantification of C, 5D and 30D. RESULTSSC/P and CSC markers expression was detected in C, 5D and 30D. Oct4, Sox2, GFRa2, Nestin and CD133 showed variations in their distribution within the gland during treatment. We observed positive cells for these markers in the marginal zone (MZ), and low immunostaining in adenohypophysis (AH) of C and 5D. In contrast, their expression was remarkable in AH of 30D, indicating a reorganization of SC from the MZ to AH. The expression levels of GFRa2, Nestin, CD133 and CD44 increased significantly in 5D compared to C and other periods of treatment. Sox2 didn´t show variations on its expression levels and the P marker Sox9, decrease in 5D. This allows to propose the participation of CS at early stage of tumor development. The pituispheres in culture were positive for SC/P and CSC markers. A significant increase of the proliferation was shown in 5D and 30D vs. C, suggesting that tumoral SC compared to C would have a different behavior due to their tumoral imprinting and participate in the neoplastic growth.