Elevated peripheral blood plasma concentrations of tie-2 and angiopoietin 2 in patients with neuroendocrine tumors

• Published in: International journal of molecular sciences Vol. 13; no. 2; pp. 1444 - 1460
• Main Authors: Melen-Mucha, Gabriela, Niedziela, Agata, Mucha, Slawomir, Motylewska, Ewelina, Lawnicka, Hanna, Komorowski, Jan, Stepien, Henryk
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-02-2012; Molecular Diversity Preservation International (MDPI)
• Subjects: Adult; Aged; Aged, 80 and over; Ang-1; Ang-2, Tie-2; Angiogenesis; angiogenic factors; Angiopoietin-2 - blood; Biomarkers, Tumor - blood; Blood vessels; Cancer; Carcinoma, Neuroendocrine - blood; Carcinoma, Neuroendocrine - mortality; Chromogranin A - blood; Endocrinology; Endostatins - blood; Female; Growth factors; Humans; Male; Metastasis; Middle Aged; Neoplasm Metastasis; Neoplasm Proteins - blood; NET patients; Neuroendocrine tumors; Osteopontin - blood; Plasma; Receptor, TIE-2 - blood; Poland; Ang-2; Ang-1; angiogenic factors; NET patients; Tie-2
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms13021444

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.
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.
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.
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.