Examining the effects of Tie2 heterogeneity on tumour-related angiogenesis and anti-angiogenic therapy.

摘要

To better understand tumour-related angiogenesis, we used the transgenic mouse model, Tie2lacZ+/Rag1 -, to examine endothelial Tie2 heterogeneity in xenografts under various conditions as well as examine the effects of anti-angiogenic therapies. Blood vessels within normal tissues were entirely Tie2 positive, but vessels within tumours were Tie2 positive, Tie2 negative or a mosaic of Tie2 positive and negative endothelial cells. The degree of heterogeneity varied amongst tumour types, but did not vary between different implantation sites. Anti-angiogenic therapy of xenografted tumours using the Delta-Tek inhibitor resulted in tumour regression, but there were no significant changes in microvessel density or Tie2 status. Anti-angiogenic therapy of tumours using endostatin did not result in regression, nor changes in microvessel density. Since Tie2 expression is related to vessel stability and maturation, this study provides an interesting assessment of the tumour endothelium and may lead to a better understanding of both tumour biology and tumour-related angiogenesis.