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Elevated Peripheral Blood Plasma Concentrations of Tie-2 and Angiopoietin 2 in Patients with Neuroendocrine Tumors
Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Dr Sterling Str. No. 3, 91-425 Lodz, Poland
Department of Clinical Endocrinology, Chair of Endocrinology, Medical University of Lodz, Dr Sterling Str. No. 3, 91-425 Lodz, Poland
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 9 January 2012; in revised form: 19 January 2012 / Accepted: 19 January 2012 / Published: 31 January 2012
Abstract: Background: Gastro-entero-pancreatic/neuroendocrine (NET) tumors are highly vascularized neoplasms. However, our knowledge concerning circulating levels of the angiogenic factors in NET patients still remains insufficient. Methods: The aim of this study was to measure plasma concentrations of VEGF, angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2), soluble Tie-2, endostatin, osteopontin (OPN) and chromogranin A (CgA) in 36 NET patients and 16 controls. Results: Only the plasma concentrations of Tie-2 and CgA were higher in NET patients as compared to controls. These levels were within the reference range in controls; however one control demonstrated slightly elevated Tie-2 and 4 elevated CgA. Similarly, in the subgroup of patients with carcinoid syndrome, only Tie-2 and CgA concentrations were higher than those in patients with non-functioning NETs. In turn, in the subgroup of metastatic patients, only Ang-2 levels were higher than in those with localized disease. A positive correlation was found between Ang-2 and Tie-2 levels in metastatic patients and between Ang-1 and Tie-2 in localized NETs. Conclusions: The plasma concentration of Tie-2 is proposed as an additional marker for NET patients and seems to be similarly effective as the currently used CgA level. Moreover, higher plasma levels of Ang-2 together with the positive correlation between Ang-2 and Tie-2 levels in metastatic subjects, implies that cases with a Tie-2 level above the upper limits, together with higher level of Ang-2 seem to be highly predictive of metastases.
Keywords: angiogenic factors; NET patients; Ang-1; Ang-2, Tie-2
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Melen-Mucha, G.; Niedziela, A.; Mucha, S.; Motylewska, E.; Lawnicka, H.; Komorowski, J.; Stepien, H. Elevated Peripheral Blood Plasma Concentrations of Tie-2 and Angiopoietin 2 in Patients with Neuroendocrine Tumors. Int. J. Mol. Sci. 2012, 13, 1444-1460.
Melen-Mucha G, Niedziela A, Mucha S, Motylewska E, Lawnicka H, Komorowski J, Stepien H. Elevated Peripheral Blood Plasma Concentrations of Tie-2 and Angiopoietin 2 in Patients with Neuroendocrine Tumors. International Journal of Molecular Sciences. 2012; 13(2):1444-1460.
Melen-Mucha, Gabriela; Niedziela, Agata; Mucha, Slawomir; Motylewska, Ewelina; Lawnicka, Hanna; Komorowski, Jan; Stepien, Henryk. 2012. "Elevated Peripheral Blood Plasma Concentrations of Tie-2 and Angiopoietin 2 in Patients with Neuroendocrine Tumors." Int. J. Mol. Sci. 13, no. 2: 1444-1460.