Barrett's mucosa: remodelling by the microenvironment.
Barrett's metaplasia and the associated adenocarcinoma are composed not only of epithelial cells, but also of inflammatory cells and endothelial cells in the lamina propria and around the tumour, respectively. The early incidence of vascular invasion and metastasis is a feature of Barrett's adenocarcinomas. A paper in this issue of The Journal of Pathology shows that vascular endothelial growth factor (VEGF) is expressed in both metaplastic cells and endothelial cells of pre-neoplastic Barrett's epithelium early in the development of neoplasia. It is becoming clearer that the harmful insults of acid and bile reflux alter not only the epithelium, but also the lamina propria. Cytokines such as tumour necrosis factor alpha (TNFalpha) or transforming growth factor (TGFalpha) are implicated in the formation of early Barrett's adenocarcinomas. From current knowledge it is possible to hypothesize that metaplastic cells, perhaps as a consequence of either TNFalpha or TGFalpha stimulation, secrete VEGF. VEGF can promote adjacent endothelial cell growth through phosphorylation of beta-catenin and vascular endothelial cadherin (VE-cadherin) in endothelial cells. In this de novo microenvironment, angiogenesis is therefore accelerated, enhancing the chance of microvascular invasion.
Harrison
R F
RF
Perry
I
I
Jankowski
J A
JA
D001471:Barrett Esophagus / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism*; D006801:Humans; D008222:Lymphokines / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors