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

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 (p85αsubunit) 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 ± 19 vs 34 ± 17 %, P < 0.01), the pAkt(+ve) cells greater than PI3K(+ve) cells (39 ± 16.0 vs 1.3 ± 0.5 %, P < 0.001), and the STAT3(+ve) cells greater than active pSTAT3(+ve) cells (14 ± 8 vs 7 ± 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 ± 7 and 7 ± 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.

• Authors: Maria Trovato, Maria Luisa Torre, Marta Ragonese, Angela Simone, Rosy Scarfì, Valeria Barresi, Giuseppe Giuffrè, Salvatore Benvenga, Flavio F Angileri, Giovanni Tuccari, Francesco Trimarchi, Rosaria Maddalena Ruggeri, Salvatore Cannavò
• Journal: Endocrine (Endocrine) Vol. 44 Issue 3 Pg. 735-43 (Dec 2013) ISSN: 1559-0100 [Electronic] United States
• PMID: 23576023 (Publication Type: Journal Article)

Chemical References

• HGF protein, human
• STAT3 Transcription Factor
• Hepatocyte Growth Factor
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-met
• Proto-Oncogene Proteins c-akt

Topics

• Adenoma (metabolism)
• Adolescent
• Adult
• Aged
• Endothelial Cells (metabolism)
• Female
• Hepatocyte Growth Factor (metabolism)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Pituitary Neoplasms (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-met (metabolism)
• STAT3 Transcription Factor (metabolism)