The Angiopoietins, Tie2 and Vascular Endothelial Growth Factor Are Differentially Expressed in the Transformation of Normal Lung to Non-small Cell Lung Carcinomas

The successful establishment of angiogenesis depends on a complex process of endothelial proliferation and organization. The angiopoietins (Ang-1 and Ang-2) and Tie2 ligand-receptor system is essential for the regulation of vascular maturation and stability during embryonic development. Together with the vascular endothelial growth factor (VEGF)-mediated pathway, they have been implicated in the control of normal physiological angiogenesis. We investigated their potential role and interaction in the development of lung cancers by comparing the expression pattern and inter-relationship of Ang-1 and 2, Tie2 and VEGF levels in 28 pairs of primary non-small cell lung cancers (NSCLC) and normal lung. Using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in-situ hybridization (ISH), we showed that in NSCLC, there was significantly up-regulated VEGF expression by the tumour cells and an increased intensity of Ang-2 expression in the tumour vessels. The number of Ang-2-expressing vessels also correlated with the grades of tumour cell expression of VEGF. On the other hand, normal lung expressed constitutively high and correlated levels of Ang-1 and Tie2, which were significantly reduced in the carcinomas. The findings suggested a role of the Ang-1/Tie2 pathway in the maintenance of the complex vasculature in normal lung, while collaborative activities between the Ang-2 and VEGF pathways might be important in promoting tumour angiogenesis in NSCLC.