Although the function of Tie2 and its ligands in tumor angiogenesis remains a subject of speculation, our findings are in agreement with a recently proposed hypothesis that in the presence of VEGF, local production of Ang-2 might promote angiogenesis.
Angiopoietin-2 (Ang-2), a ligand of the endothelial tyrosine kinaseTie-2, is emerging as a key regulator of vascular remodeling during tumor angiogenesis.
Blockade of both VEGF-R2 and Tie-2 pathways simultaneously or the VEGF receptor pathway alone resulted in a significant inhibition of tumor growth and tumor angiogenesis (92.2% and 74.4%, respectively).
In contrast, human Tie-2-monospecific pAd-1S05 intrabody did not affect the growth of tumors, indicating that the antitumor effect of pAd-2S03 was due to the inhibition of tumor angiogenesis in these murine models.
In this study, we investigated the expression of Ang-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in surgically resected specimens from 46 patients with HCC to determine their potential role in tumor angiogenesis and its progression.
Inhibition of the VEGF/VEGF receptor (VEGFR) and angiopoietin-2 (Ang-2)/TEK receptor tyrosine kinase (Tie-2) pathway is a potential target for tumor angiogenesis.
Nude mouse xenografts revealed that interference with either the VEGF receptor pathway or the Tie-2 pathway resulted in a significant inhibition of tumor growth and tumor angiogenesis.
Real-Time PCR, Western Blot and Immunofluorescence staining showed that plumbagin treatment suppressed expression of angiogenesis pathways (PI3K-Akt, VEGF/KDR and Angiopoietins/Tie2) and angiogenic factors (VEGF, CTGF, ET-1, bFGF),which is associated with tumor angiogenesis in cancer cells and xenograft tumor tissues.
Recently, Tie2-expressing macrophages (TEM) have been identified as a distinct sub-population influencing tumor angiogenesis and vascular remodeling as well as monocyte differentiation.
The essential roles of Ang-1 and Tie-2 in embryonic angiogenesis have been established, and studies have demonstrated the involvement of Ang-1 and Ang-2 in tumor angiogenesis.
The system involving angiopoietin-2 (Ang-2) and its receptor, Tie-2, appears to play an important role not only in tumor angiogenesis, but also in the biology of haematological and non-haematological malignancies.
These results suggest that the angiopoietin/Tie-2 system may participate in the angiogenic response to hypoxia in renal tissues and in tumor angiogenesis in renal carcinoma.