Motility factors identified in supernatants of human cholangiocarcinoma cell lines

Steffen, Martín; Zuehlke, Isabel; Scherdin, Ulrich

doi:10.3892/ijo.18.5.1107

Cited by 5 publications

(3 citation statements)

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“…The nine human biliary cancer cell lines used for this study included EGI-1 and TFK-1 9,10 (obtained from the German Collection of Microorganisms and Cell Cultures Department, Braunschweig, Germany), HUH28 11 and HUCCT-1 12 (obtained from the Health Science Research Resources Bank, Osaka, Japan), SNU 245, SNU 308, and SNU 1079 13 (obtained from the Korean Cell Line Bank, Seoul, Korea), GB-H3, and GB-D1.…”

Section: Non-neoplastic Epithelial Scrapings Primary Biliary Cancersmentioning

confidence: 99%

Identification of Novel Cellular Targets in Biliary Tract Cancers Using Global Gene Expression Technology

Hansel

Rahman

Hidalgo

et al. 2003

The American Journal of Pathology

116

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Biliary tract carcinoma carries a poor prognosis, and difficulties with clinical management in patients with advanced disease are often due to frequent late-stage diagnosis, lack of serum markers, and limited information regarding biliary tumor pathogenesis. RNAbased global analyses of gene expression have led to the identification of a large number of up-regulated genes in several cancer types. We have used the recently developed Affymetrix U133A gene expression microarrays containing nearly 22,000 unique transcripts to obtain global gene expression profiles from normal biliary epithelial scrapings (n ‫؍‬ 5), surgically resected biliary carcinomas (n ‫؍‬ 11), and biliary cancer cell lines (n ‫؍‬ 9). Microarray hybridization data were normalized using dCHIP (http://www.dCHIP.org) to identify differentially up-regulated genes in primary biliary cancers and biliary cancer cell lines and their expression profiles was compared to that of normal epithelial scrapings using the dCHIP software as well as Significance Analysis of Microarrays or SAM (http:// www-stat.stanford.edu/ϳtibs/SAM/). Comparison of the dCHIP and SAM datasets revealed an overlapping list of 282 genes expressed at greater than threefold levels in the cancers compared to normal epithelium (t-test P <0.1 in dCHIP, and median false discovery rate <10 in SAM). Several pathways integral to tumorigenesis were up-regulated in the biliary cancers, including proliferation and cell cycle antigens (eg, cyclins D2 and E2, cdc2/p34, and geminin), transcription factors (eg, homeobox B7 and islet-1), growth factors and growth factor receptors (eg, hepatocyte growth factor, amphiregulin, and insulin-like growth factor 1 receptor), and enzymes modulating sensitivity to chemotherapeutic agents (eg, cystathionine ␤ synthase, dCMP deaminase, and CTP synthase). In addition, we identified several "pathway" genes that are rapidly emerging as novel therapeutic targets in cancer (eg, cytosolic phospholipase A2, an upstream target of the cyclooxygenase pathway, and ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E, two important downstream mediators of the mitogenic Akt/mTOR signaling pathway). Overexpression of selected up-regulated genes was confirmed in tissue microarrays of biliary cancers by immunohistochemical analysis (n ‫؍‬ 4) or in situ hybridization (n ‫؍‬ 1), and in biliary cancer cell lines by reverse transcriptase PCR (n ‫؍‬ 2). The majority of genes identified in the present study has not been previously reported in biliary cancers, and represent novel potential screening and therapeutic targets of this cancer type. Biliary tract carcinomas, which include cancers of the gallbladder and intra-and extrahepatic biliary tree, affect 7500 individuals in the United States each year, and nearly 3500 patients die as a direct consequence of this lethal disease.1 Once established, biliary tract cancers are notoriously challenging to diagnose and treat. At present, only surgical excision of detectable malignancy is associated with improvement in ...

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Section: Non-neoplastic Epithelial Scrapings Primary Biliary Cancersmentioning

confidence: 99%

Identification of Novel Cellular Targets in Biliary Tract Cancers Using Global Gene Expression Technology

Hansel

Rahman

Hidalgo

et al. 2003

The American Journal of Pathology

116

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“…High level expression of HCV-C in hilar cholangiocarcinoma tissues indicated that HCV-C protein play an important role in the process of cancer cells inversion and proliferation, through some direct or indirect effects on certain oncogenes, tumor suppressor genes and cell apoptosis (3). However, in most of the pervious studies, cholangiocarcinoma cell lines, but not normal biliary tract endothelial cells, were used to investigate the mechanism of cholangiocarcinoma generation (4)(5)(6). In this study, a human normal biliary tract endothelial cell (hBEC) line was used to investigate the tumorigenesis ability of HCV-C and its potential mechanism.…”

Section: Introductionmentioning

confidence: 99%

Malignant transformation of the cultured human normal biliary tract epithelial cells induced by hepatitis C virus core protein

Chen

Li²,

Liu³

et al. 2007

Oncol Rep

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High level expression of hepatitis C virus core protein (HCV-C) was detected in hilar cholangiocarcinoma tissues in our previous studies. This protein played an important role in the process of cancer cell inversion and proliferation, by some direct and indirect effects on certain genes. Based on this observation, we investigated the effect of HCV-C on human normal biliary epithelial (hBE) cell transformation and tumor development. Plasmid pHCV-C encoding the gene of HCV core protein was constructed and transfected into hBE cells. The expression and the biological effect of HCV-C in HCV-C gene-modified hBE cells were determined in vitro and in vivo. The clone formation rates of hBE cells transfected with pHCV-C, pcDNA3.1 and mocktransfected cells were 36, 2.5 and 1.5%, respectively. Tumor developed in 7 of 7 nude mice after incubated with pHCV-C transfected hBE cells, while no tumor appeared in mice injected with pcDNA3.1-and mock-transfected hBE cells. To investigate the possible mechanism of malignant transformation, we further studied the telomerase activity and human telomerase reverse transcriptase (hTERT) expression in pHCV-C transfected hBE cells. The elevated expression of hTERT was confirmed by RT-PCR, immunocytochemistry (ICC) and Western blot analysis, which in turn elevated the telomerase activity, confirmed by TRAP-ELISA. These results indicated that HCV-C protein could participate in malignant transformation of human normal biliary epithelial cells and induce cholangiocarcinoma tumorigenesis, and the activation of telomerase was one of the possible mechanisms.

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“…Particularly, HGF promotes tumor metastasis by stimulating motility and invasion, likely through a number of mechanisms, including decreased cell-cell adhesion, enhanced cell motility, and upregulated proteolytic activity in matrix metalloproteases (MMPs). [2][3][4] The pleiotropic cellular effects of HGF are transduced through activation of its transmembrane receptor tyrosine kinase c-Met, which is a product of the c-met proto-oncogene. 5 On HGF binding, c-Met undergoes dimerization and autophosphorylation on tyrosine residues, generating multidocking sites, which activate diverse intracellular signaling pathways.…”

mentioning

confidence: 99%

Involvement of PI3K/Akt Signaling Pathway in Hepatocyte Growth Factor–Induced Migration of Uveal Melanoma Cells

et al. 2008

Invest. Ophthalmol. Vis. Sci.

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Motility factors identified in supernatants of human cholangiocarcinoma cell lines

Cited by 5 publications

References 0 publications

Identification of Novel Cellular Targets in Biliary Tract Cancers Using Global Gene Expression Technology

Identification of Novel Cellular Targets in Biliary Tract Cancers Using Global Gene Expression Technology

Malignant transformation of the cultured human normal biliary tract epithelial cells induced by hepatitis C virus core protein

Involvement of PI3K/Akt Signaling Pathway in Hepatocyte Growth Factor–Induced Migration of Uveal Melanoma Cells

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