Urokinase type plasminogen activator receptor expression in colorectal neoplasms.
BACKGROUND
The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis.


OBJECTIVE
To study the involvement of uPAR in colorectal carcinogenesis.


METHODS
The cellular expression and localisation of uPAR were investigated in colorectal adenomas and invasive carcinomas by in situ hybridisation, immunohistochemistry, and northern and western blot analyses.


RESULTS
uPAR mRNA expression was found mainly in the cytoplasm of dysplastic epithelial cells of 30% of adenomas with mild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes' stages A (72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPAR was detected in dysplastic epithelial cells of 14% of adenomas and in carcinomatous cells of 49% of invasive carcinomas. uPAR mRNA and protein concentrations were significantly higher in severe than in mild or moderate dysplasia (p<0.05); they were notably higher in Dukes' stage A than in severe dysplasia (p<0.05), and significantly higher in Dukes' stage B than in stage A (p<0.05), but those in stage B were not different from those in stage C or in metastatic colorectal carcinomas of the liver.


CONCLUSIONS
Colorectal adenoma uPAR, expressed essentially in dysplastic epithelial cells, was upregulated with increasing severity of atypia, and increased notably during the critical transition from severe dysplasic adenoma to invasive carcinoma. These findings implicate uPAR expression in the invasive and metastatic processes of colorectal cancer.
Suzuki
S
S
First Division of Pathology, Kobe University School of Medicine, Kobe, Japan.
Hayashi
Y
Y
Wang
Y
Y
Nakamura
T
T
Morita
Y
Y
Kawasaki
K
K
Ohta
K
K
Aoyama
N
N
Kim
S R
SR
Itoh
H
H
Kuroda
Y
Y
Doe
W F
WF
D015152:Blotting, Northern; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator
D009363:Neoplasm Proteins; C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators