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.
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.
Aliev
G
G
Department of Neurology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. gxa15@po.cwru.edu
Smith
M A
MA
Seyidova
D
D
Neal
M L
ML
Shi
J
J
Loizidou
M
M
Turmaine
M
M
Friedland
R P
RP
Taylor
I
I
Burnstock
G
G
Perry
G
G
Lamanna
J C
JC
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*
D019332:Endothelin-1; D019001:Nitric Oxide Synthase