Urokinase type plasminogen activator receptor expression in colorectal neoplasms - PubMed (original) (raw)

. 1998 Dec;43(6):798-805.

doi: 10.1136/gut.43.6.798.

Y Hayashi, Y Wang, T Nakamura, Y Morita, K Kawasaki, K Ohta, N Aoyama, S R Kim, H Itoh, Y Kuroda, W F Doe

Affiliations

Urokinase type plasminogen activator receptor expression in colorectal neoplasms

S Suzuki et al. Gut. 1998 Dec.

Abstract

Background: The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis.

Aims: 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.

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Figures

Figure 1

Figure 1

Localisation of uPAR gene transcript in colorectal neoplasms. (A) mild dysplasia: uPAR mRNA is present diffusely or focally in whole adenomas. (C) moderate dysplasia: uPAR mRNA shows mainly in the cytoplasm of dysplastic cells (arrowheads) and is faint in the cytoplasm of stromal cells (straight arrows) in adenomas. (E) invasive carcinoma: uPAR mRNA is strongly expressed in malignant cells on the surface of cancerous tissue, predominantly at the invasive front of the tumour (arrowheads). (B, D, F): no staining was detected with the sense riboprobe in adjacent sections.

Figure 2

Figure 2

(A) Representative northern blot analysis of uPAR gene transcript in colorectal neoplasms. Lane 1, normal colorectal tissue; lanes 2, 3, 4, mild dysplasia; lanes 5, 6, moderate dysplasia; lanes 7, 8, severe dysplasia; lane 9, Dukes' stage A carcinoma; lane 10, Dukes' stage B carcinoma; lane 11, Dukes' stage C carcinoma; lane 12, metastatic carcinoma of the liver. The position of 18S rRNA (1.86Kb) is indicated. (B) Representative western blot analysis of uPAR in extracts from colorectal neoplasms with antibody no. 3937. Lane 1, normal colorectal tissue; lanes 2, 3, 4, mild dysplasia; lanes 5, 6, moderate dysplasia; lanes 7, 8, severe dysplasia; lane 9, Dukes' stage A carcinoma; lane 10, Dukes' stage B carcinoma; lane 11, Dukes' stage C carcinoma; lane 12, metastatic carcinoma of the liver. The relative position of molecular weight marker (kDa) is indicated on the left.

Figure 3

Figure 3

Densitometric analysis. uPAR mRNA and protein concentrations seen on northern blots, normalised with β actin, and western blots were quantified as the ratio of those in mild dysplasic adenoma. Results are expressed as mean (SEM). *p<0.05 compared with moderate dysplasia; †p<_0.05 compared with severe dysplasia;‡_p<0.05 compared with Dukes' stage A.

Figure 4

Figure 4

Immunohistochemical localisation of uPAR protein in colorectal neoplasms. (A) Faint staining was seen in the dysplastic proliferative epithelium of adenomas (arrowheads) but not in normal glands (straight arrow). (B) Intense staining was localised in carcinomatous cells, predominantly at the invasive front of the carcinoma. Immunoreactivity was detected at the plasma membrane and cytoplasm of dysplastic or carcinomatous cells. Very few or no stromal cells associated with tumours were positive.

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