Correlation between the overexpression of urokinase receptor isoform uPAR (D1D2) and hepatic cell malignant 
transformation

Zhou,Yingqun; Lǚ,Xiaoping; Li,Shan; Zhan,Lingling

doi:10.3892/mmr.2014.2006

May-2014 Volume 9 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

May-2014 Volume 9 Issue 5

Full Size Image

Article

Correlation between the overexpression of urokinase receptor isoform uPAR (D1D2) and hepatic cell malignant transformation

Authors:
- Yingqun Zhou
- Xiaoping Lǚ
- Shan Li
- Lingling Zhan
View Affiliations / Copyright

Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Pages: 1689-1696
|
Published online on: March 4, 2014

https://doi.org/10.3892/mmr.2014.2006
Expand metrics +

Abstract

In order to provide an abundant source of specimen and to reveal the correlation between the overexpression of urokinase plasminogen activator receptor isoform uPAR (D1D2) and hepatic cell malignant transformation, the optimal liver cell culture method was selected from three cell culture methods to culture and separate out liver cells with a high density, high purity and high activity. The specimens were used to culture and assess the uPAR (D1D2) mRNA level in normal liver cells, liver cancer cells and para-carcinoma cells. In the present study, the correlation between the overexpression of uPAR (D1D2) and hepatic cell malignant transformation was discussed. When comparing the tissue block adherent method, liver cell grinding method and pancreatic enzyme digestion method, the liver tissue adherent method was found to be economical, simple and overall the optimal method for liver cell culture. This was used as a reference standard for cell culture. RT-PCR was used to determine isoform uPAR (D1D2) mRNA level in normal liver cells, para-carcinoma cells and liver cancer cells. The comparison of uPAR (D1D2) mRNA levels in normal liver cells, para-carcinoma cells and liver cancer cells, demonstrated that the brightness of the cells clearly increased in normal liver cells, para-carcinoma cells and liver cancer cells. The comparison of the cell grey values of three groups demonstrated a statistically significant difference (P<0.05). The liver tissue adherent method was able to produce liver cells with a high density, high purity and high activity, providing a sufficient source of specimen for our subsequent experiments. The electrophoresis results showed that: uPAR (D1D2) mRNA expression increased from normal liver cells to para-carcinoma cells to liver cancer cells, inferring that uPAR (D1D2) mRNA overexpression may be the result of changes in the conformation of the uPAR isoform. In addition, it is closely associated with abnormal cell signal transduction, which leads to clonal proliferation and abnormal differentiation of liver cells with malignant transformation in liver cells.

View Figures

View References

1	Mondino A and Blasi F: uPA and uPAR in fibrinolysis, immunity and pathology. Trends Immunol. 25:450–455. 2004. View Article : Google Scholar : PubMed/NCBI
2	Blasi F and Carmeliet P: uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 3:932–943. 2002. View Article : Google Scholar : PubMed/NCBI
3	Piironen T, Laursen B, Pass J, et al: Specific immunoassays for detection of intact and cleaved forms of the urokinase receptor. Clin Chem. 50:2059–2068. 2004. View Article : Google Scholar : PubMed/NCBI
4	Behrendt N, Ploug M, Patthy L, et al: The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator. J Biol Chem. 266:7842–7847. 1991.PubMed/NCBI
5	Behrendt N, Ronne E and Dano K: Domain interplay in the urokinase receptor. Requirement for the third domain in high affinity ligand binding and demonstration of ligand contact sites in distinct receptor domains. J Biol Chem. 271:22885–22894. 1996. View Article : Google Scholar
6	Stewart CE and Sayers I: Characterisation of urokinase plasminogen activator receptor variants in human airway and peripheral cells. BMC Mol Biol. 10:752009. View Article : Google Scholar : PubMed/NCBI
7	Andreasen PA, Kjøller L, Christensen L, et al: The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer. 72:1–22. 1997. View Article : Google Scholar : PubMed/NCBI
8	Guo Z, Yang X, Sun F, et al: A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res. 69:2305–2313. 2009. View Article : Google Scholar : PubMed/NCBI
9	Fackenthal JD and Godley LA: Aberrant RNA splicing and its functional consequences in cancer cells. Dis Model Mech. 1:37–42. 2008. View Article : Google Scholar : PubMed/NCBI
10	Keren H, Lev-Maor G and Ast G: Alternative splicing and evolution: diversification, exon definition and function. Nat Rev Genet. 11:345–355. 2010. View Article : Google Scholar : PubMed/NCBI
11	Bjarnadóttir TK, Geirardsdóttir K, Ingemansson M, et al: Identification of novel splice variants of Adhesion G protein-coupled receptors. Gene. 387:38–48. 2007.PubMed/NCBI
12	Sato S, Kopitz C, Grismayer B, et al: Overexpression of the urokinase receptor mRNA splice variant uPAR-del4/5 affects tumor-associated processes of breast cancer cells in vitro and in vivo. Breast Cancer Res Treat. 127:649–657. 2011. View Article : Google Scholar : PubMed/NCBI
13	Zhan L, Lv X, Li S, Jiang H, Zuo J and Tang J: The correlation of liver cirrhosis plasma, uPA, uPAR level between liver fibrosis and carcinogenesis. J Clin Lab Sci. 26:144–145. 2008.(In Chinese).
14	Chu CJ, Hussain M and Lok AS: Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology. 36:1408–1415. 2002. View Article : Google Scholar : PubMed/NCBI
15	Su Q, Schröder CH, Hofmann WJ, et al: Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinomas. Hepatology. 27:1109–1120. 1998. View Article : Google Scholar : PubMed/NCBI
16	Mazzieri R and Blasi F: The urokinase receptor and the regulation of cell proliferation. Thromb Haemost. 93:641–646. 2005.PubMed/NCBI
17	Luther T, Kotzsch M, Meye A, et al: Identification of a novel urokinase receptor splice variant and its prognostic relevance in breast cancer. Thromb Haemost. 89:705–717. 2003.PubMed/NCBI
18	Thurison T, Lomholt AF, Rasch MG, et al: A new assay for measurement of the liberated domain I of the urokinase receptor in plasma improves the prediction of survival in colorectal cancer. Clin Chem. 56:1636–1640. 2010. View Article : Google Scholar : PubMed/NCBI