Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Dec;53(6):307-12.
doi: 10.1136/mp.53.6.307.

Plasminogen activator system, vascular endothelial growth factor, and colorectal cancer progression

E A Baker  1 , F G Bergin, D J Leaper
Affiliations

Plasminogen activator system, vascular endothelial growth factor, and colorectal cancer progression

E A Baker et al. Mol Pathol. 2000 Dec.

Abstract

Aims: To plasminogen activator system (PAS) consists of the plasminogen activators (urokinase (uPA) and tissue-type (tPA) plasminogen activators), the uPA receptor (uPAR), and the plasminogen activator inhibitors (PAI-1 and PAI-2). Plasminogen activators activate plasminogen to plasmin, which can break down extracellular matrix (ECM) components. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and is involved in angiogenesis. VEGF has been shown to upregulate uPA and this may facilitate tumour angiogenesis further.

Methods: PAS components and VEGF were determined by enzyme linked immunosorbent assay (ELISA) in paired colorectal tumour and normal tissue (n = 50) and correlated with pathological staging.

Results: uPA, uPAR, PAI-1, and VEGF values were significantly higher in tumour tissue (for example, tumour uPA: median, 2.3 (range, 0.1-6.7) ng/mg protein v normal uPA: median, 0.2 (range, 0-2.6) ng/mg protein). tPA was significantly higher in normal mucosa and there was no difference in PAI-2. uPA, uPAR, PAI-1, and VEGF values significantly correlated with each other and with Dukes's staging (uPA in adenomas: median, 0.42 (range, 0.1-1.2) ng/mg protein; upA in Dukes's B tumours: median, 2.1 (range, 0.4-4.3) ng/mg protein; and uPA in Dukes's D tumours: median, 4.0 (range, 3.7-4.2) ng/mg protein) and lymphatic invasion. In addition PAI-1 also correlated with tumour size and differentiation.

Conclusion: The involvement of the PAS and VEGF in colorectal cancer appears to be complex. uPA, uPAR, PAI-1, and VEGF were upregulated in tumour tissue and this correlated with Dukes's staging and lymphatic invasion.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Box plots showing the positive correlation between (A) urokinase plasminogen activator (uPA), (B) the uPA receptor (uPAR), (C) plasminogen activator inhibitor 1 (PAI-1), and (D) vascular endothelial growth factor (VEGF) values with the Dukes's stage of the tumour (median and interquartile range) in colorectal cancer tissue (*p < 0.05, Spearman's correlation). The line within the box plot corresponds to the median value.
Figure 2
Figure 2
Box plots showing the positive correlations between (A) urokinase plasminogen activator (uPA), (B) the uPA receptor (uPAR), (C) plasminogen activator inhibitor 1 (PAI-1), and (D) vascular endothelial growth factor (VEGF) values and lymphatic invasion (median and interquartile range). Expression was significantly greater in tumours that had undergone lymphatic invasion (*p < 0.05, Spearman's correlation). The line within the box plot corresponds to the median value.
Figure 3
Figure 3
Box plots showing the positive correlation between plasminogen activator inhibitor 1 (PAI-1) values and (A) tumour differentiation and (B) tumour size (median and interquartile range). * p < 0.05 Spearman's correlation. The line within the box plot corresponds to the median value.
See this image and copyright information in PMC

References

    1. Folkmann J. What is the evidence that tumours are angiogenesis dependent? J Natl Cancer Inst 1990;82:4–6. - PubMed
    1. Folkmann J, Shing Y. Angiogenesis. J Biol Chem 1992;267:10931–4. - PubMed
    1. Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis and proliferation of human colon cancer. Cancer Res 1995;55:3964–8. - PubMed
    1. Kang SM, Maeda K, Chung YS, et al. Vascular endothelial growth factor expression correlates with haematogenous metastasis and prognosis in colorectal carcinoma. Oncol Rep 1997;4:381–4. - PubMed
    1. Ferrara N, Houck K, Jakeman L, et al. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 1992;13:18–32. - PubMed

MeSH terms

Substances