The ligand/receptor hepatocyte growth factor (HGF)/c-met signaling system promotes cellular growth and angiogenesis through PI3K/phosphor-Akt and STAT3/phosphor-STAT3 downstream effectors. In this study, we have evaluated the expression of molecules of the HGF/c-met pathway in pituitary adenomas (PA). The expression of HGF, c-met, PI3K (p85 alpha subunit) pAkt, STAT3, and pSTAT3 was analyzed by immunohistochemistry in an archival series of 30 PA (12 non-functioning and 18 functioning; 25 macroadenomas and 5 microadenomas). PAs expressed all six proteins in tumor epithelial cells. The proportion of c-met(+ve) cells was greater than HGF(+ve) cells (49 +/- A 19 vs 34 +/- A 17 %, P < 0.01), the pAkt(+ve) cells greater than PI3K(+ve) cells (39 +/- A 16.0 vs 1.3 +/- A 0.5 %, P < 0.001), and the STAT3(+ve) cells greater than active pSTAT3(+ve) cells (14 +/- A 8 vs 7 +/- A 6 %, P < 0.01). Furthermore, endothelial Akt immunostaining was detected on the vascular surface area of 17 PAs, in macroadenomas more frequently than in microadenomas (82 vs 18 %). The percentage of immunostained endothelial cells was greater in macro than in microadenomas (19 +/- A 7 and 7 +/- A 3 %; P < 0.05). In conclusion, HGF and c-met are widely expressed in PA, and correlate with pAkt expression. These data, together with the finding of pAkt immunostaining on microvascular areas related to tumor size, suggest a major role of the pAKT signaling in tumor growth and angiogenesis. There might be practical implications for the targeted therapy of PA.

HGF/c-met system targeting PI3K/AKT and STAT3/phosphorylated-STAT3 pathways in pituitary adenomas: an immunohistochemical characterization in view of targeted therapies

Barresi V;
2013-01-01

Abstract

The ligand/receptor hepatocyte growth factor (HGF)/c-met signaling system promotes cellular growth and angiogenesis through PI3K/phosphor-Akt and STAT3/phosphor-STAT3 downstream effectors. In this study, we have evaluated the expression of molecules of the HGF/c-met pathway in pituitary adenomas (PA). The expression of HGF, c-met, PI3K (p85 alpha subunit) pAkt, STAT3, and pSTAT3 was analyzed by immunohistochemistry in an archival series of 30 PA (12 non-functioning and 18 functioning; 25 macroadenomas and 5 microadenomas). PAs expressed all six proteins in tumor epithelial cells. The proportion of c-met(+ve) cells was greater than HGF(+ve) cells (49 +/- A 19 vs 34 +/- A 17 %, P < 0.01), the pAkt(+ve) cells greater than PI3K(+ve) cells (39 +/- A 16.0 vs 1.3 +/- A 0.5 %, P < 0.001), and the STAT3(+ve) cells greater than active pSTAT3(+ve) cells (14 +/- A 8 vs 7 +/- A 6 %, P < 0.01). Furthermore, endothelial Akt immunostaining was detected on the vascular surface area of 17 PAs, in macroadenomas more frequently than in microadenomas (82 vs 18 %). The percentage of immunostained endothelial cells was greater in macro than in microadenomas (19 +/- A 7 and 7 +/- A 3 %; P < 0.05). In conclusion, HGF and c-met are widely expressed in PA, and correlate with pAkt expression. These data, together with the finding of pAkt immunostaining on microvascular areas related to tumor size, suggest a major role of the pAKT signaling in tumor growth and angiogenesis. There might be practical implications for the targeted therapy of PA.
2013
HGF/c-met signaling; STAT3/pSTAT3; PI3K; pAKT; Pituitary adenomas; Adenoma; Adolescent; Adult; Aged; Endothelial Cells; Female; Hepatocyte Growth Factor; Humans; Immunohistochemistry; Male; Middle Aged; Phosphatidylinositol 3-Kinases; Phosphorylation; Pituitary Neoplasms; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-met; STAT3 Transcription Factor
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/986380
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