This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, T. Articles by Tang, Z.-Y. Search for Related Content PubMed PubMed Citation Articles by Zhang, T. Articles by Tang, Z.-Y.

Overexpression of Platelet-Derived Growth Factor Receptor in Endothelial Cells of Hepatocellular Carcinoma Associated with High Metastatic Potential

Authors' Affiliation: Liver Cancer Institute and Zhong Shan Hospital of Fudan University, Shanghai, People's Republic of China

Requests for reprints: Zhao-You Tang, Liver Cancer Institute and Zhong Shan Hospital of Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, People's Republic of China. Phone: 86-21-6403-7181; Fax: 86-21-6403-7181; E-mail: zytang{at}scrap.stc.sh.cn.

Purpose: Little information is available on the heterogeneity of the vascular endothelium in hepatocellular carcinoma. The aim of this study was to identify the differentially expressed genes in tumor endothelial cells from highly metastatic hepatocellular carcinoma.

Experimental Design: Magnetic beads conjugated with anti-CD31 antibody were used to isolate vascular endothelial cells from hepatocellular carcinoma xenografts with different metastatic potentials in nude mice. Gene expression profiles for different endothelial cells were compared by use of cDNA microarray. The up-regulated gene was confirmed by reverse transcription-PCR, real-time PCR, and immunohistochemistry.

Results: cDNA microarray analysis revealed differential expression patterns in seven genes consistently presented in endothelial cells isolated from hepatocellular carcinoma with different metastatic potentials. Overexpression of platelet-derived growth factor receptor was found only in the endothelium of highly metastatic hepatocellular carcinoma, which was confirmed by reverse transcription-PCR, real-time PCR, and immunohistochemistry. Oral administration of STI571 (imatinib mesylate or Glivec), a protein tyrosine kinase inhibitor of platelet-derived growth factor receptor, combined with s.c. injection of IFN- not only effectively reduced tumor weight (by 81.8%) and microvessel density (by 70.2%) but also inhibited lung metastasis (by 100%). Furthermore, immunohistochemical analysis of platelet-derived growth factor receptor in human hepatocellular carcinoma tissues revealed its correlation with postoperative recurrence, especially in patients without microvessel invasion.

Conclusions: The gene expression of hepatocellular carcinoma vascular endothelium is different between tumors with different metastatic potential. Platelet-derived growth factor receptor , which is overexpressed in endothelium of highly metastatic hepatocellular carcinoma, may serve as a biomarker for predicting metastasis and a therapeutic target for highly metastatic hepatocellular carcinoma.

This article has been cited by other articles:

				P. Stock, D. Monga, X. Tan, A. Micsenyi, N. Loizos, and S. P.S. Monga Platelet-derived growth factor receptor-{alpha}: a novel therapeutic target in human hepatocellular cancer Mol. Cancer Ther., July 1, 2007; 6(7): 1932 - 1941. [Abstract] [Full Text] [PDF]