title: Increased expression of NOS and ET-1 immunoreactivity in human colorectal metastatic liver tumours is associated with selective depression of constitutive NOS immunoreactivity in vessel endothelium.
abstract: The absence of perivascular nerves in tumour vessels suggests that endothelium derived vasoactive substances [nitric oxide (NO) and endothelin-1 (ET-1)] may be key factors in controlling tumour blood flow during tumour growth and metastasis. We have studied the ultrastructural distribution and immunoreactivity of different NO synthase (NOS) isoforms and ET-1 in human colorectal metastatic liver tumour tissues using pre-embedding peroxidase-anti-peroxidase and post-embedding immunoelectron microscopic triple gold labelling techniques. Dramatically lower NOS 1 immunoreactivity was observed in tumour vascular endothelium (1-3% and 15-20% in tumour and normal groups, respectively). As compared to control groups there were significantly less NOS3 immunopositive EC in metastatic tumour vessels (45-50% and 1-3% in normal and tumour groups, respectively). A striking rise in NOS2 was observed in tumour vessel endothelium (< 1% in normal and 65-70% in tumour vessel endothelium). ET-1 immunoreactivity levels were also significantly higher in tumour vessel endothelium (85-90% in tumour, 15-20% in normal group). This increased expression of NOS2 and ET-1 immunoreactivity was accompanied by the increased expression of three NOS isoforms and ET-1 immunoreactivity in liver parenchymal cells. These data suggest that metastatic tumour vessel endothelium is characterized by increased expression of NOS2 and ET-1 and by decreases in NOS1 and NOS3. These characteristics are associated with the overexpression of all three NOS isoforms and ET-1 immunoreactivity in non-vascular cells.
authors: Department of Neurology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. gxa15@po.cwru.edu
authors: G
authors: G
authors: Aliev
authors: M A
authors: MA
authors: Smith
authors: D
authors: D
authors: Seyidova
authors: M L
authors: ML
authors: Neal
authors: J
authors: J
authors: Shi
authors: M
authors: M
authors: Loizidou
authors: M
authors: M
authors: Turmaine
authors: R P
authors: RP
authors: Friedland
authors: I
authors: I
authors: Taylor
authors: G
authors: G
authors: Burnstock
authors: G
authors: G
authors: Perry
authors: J C
authors: JC
authors: Lamanna
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000473:pathology*; D019332:Endothelin-1 / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D022781:Hepatocytes / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary* / Q000648:ultrastructure; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D019332:Endothelin-1; D019001:Nitric Oxide Synthase