Purpose: Hypothalamic or locally produced growth factors and cytokines control pituitary development, functioning, and cell division.We evaluated the expression of the chemokine stromal cell-derived factor 1 (SDF1) and its receptor CXCR4 in human pituitary adenomas and normal pituitary tissues and their role in cell proliferation. Experimental Design: The expression of SDF1and CXCR4 in 65 human pituitary adenomas and 4 human normal pituitarieswas determined by reverse transcription-PCR, immunohistochemistry, and confocal immunofluorescence. The proliferative effect of SDF1was evaluated in eight fibroblast-free human pituitary adenoma cell cultures. Results: CXCR4 mRNAwas expressed in 92% of growth hormone (GH)-secreting pituitary adenomas (GHoma) and 81% of nonfunctioning pituitary adenomas (NFPA), whereas SDF1 was identified in 63% and 78% of GHomas and NFPAs, respectively. Immunostaining for CXCR4 and SDF1showed a strong homogenous labeling in all tumoral cells in both GHomas and NFPAs. In normal tissues, CXCR4 and SDF1were expressed only in a subset of anterior pituitary cells,with a lower expression of SDF1compared with its cognate receptor. CXCR4 and SDF1were not confined to a specific cell population in the anterior pituitary but colocalized with discrete subpopulations of GH-, prolactin-, and adrenocorticorticotropic hormone ^ secreting cells. Conversely, most of the SDF1-containing cells expressed CXCR4. In six of eight pituitary adenoma primary cultures, SDF1induced a statistically significant increase in DNA synthesis that was prevented by the treatment with the CXCR4 antagonist AMD3100 or somatostatin. Conclusions: CXCR4 and SDF1are overexpressed in human pituitary adenomas and CXCR4 activation may contribute to pituitary cell proliferation and, possibly, to adenoma development ‘in humans.
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|Titolo:||Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas|
|Data di pubblicazione:||2008|
|Citazione:||Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas / Barbieri, Federica; Bajetto, Adriana; Stumm, R; Pattarozzi, Alessandra; Porcile, C; Zona, Gianluigi; Dorcaratto, A; Ravetti, Jl; Minuto, Francesco; Spaziante, R; Schettini, Gennaro; Ferone, Diego; Florio, Tullio. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - STAMPA. - 14(2008), pp. 5022-5032.|
|Appare nelle tipologie:||01.01 - Articolo su rivista|