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      CEACAM6 gene expression in intrahepatic cholangiocarcinoma

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          Abstract

          The purpose of this study was to investigate the clinicopathological and biological significance of human carcinoembryonic antigen-related cell adhesion molecule 6 ( CEACAM6) gene expression in human intrahepatic cholangiocarcinoma. CEACAM6 is reported to be involved in human malignancies. However, in cholangiocarcinoma expression of CEACAM6 and its clinicopathological significance have not been investigated. CEACAM6 expression status was determined and analysed with respect to various clinicopathological parameters in 23 intrahepatic cholangiocarcinomas. Additionally, we investigated effects of CEACAM6 gene in the cholangiocarcinoma cell lines. CEACAM6 gene expression in cancer tissues was higher than in noncancerous tissues in 16 of the 23 cases; however, it was not statistically significant. The tumours with elevated CEACAM6 expression showed a tendency to be associated with lymphatic invasion and stage of the disease. Interestingly, patients with high CEACAM6 expression showed a significantly poorer disease-free survival rate than those with low CEACAM6 expression. We demonstrated that CEACAM6-transfected cells were more proliferative, more invasive and more chemoresistant to gemcitabine compared to mock-transfected cells. Furthermore, CEACAM6 gene silencing by CEACAM6-specific siRNA resulted in higher chemosensitivity to gemcitabine. CEACAM6 is a potential prognostic indicator and potential chemoresistant marker to gemcitabine for patients with intrahepatic cholangiocarcinoma.

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          Cholangiocarcinoma.

          Shahid Khan, Howard C Thomas, Brian Davidson … (2005)
          Cholangiocarcinoma is a devastating malignancy that presents late, is notoriously difficult to diagnose, and is associated with a high mortality. The incidence of intrahepatic cholangiocarcinoma is increasing worldwide. The cause for this rise is unclear, although it could be related to an interplay between predisposing genetic factors and environmental triggers. MRI and CT with endoscopic ultrasound and PET provide useful diagnostic information in certain patients. Surgical resection is the only chance for cure, with results depending on careful technique and patient selection. Data suggest that liver transplantation could offer long-term survival in selected patients when combined with neoadjuvant chemoradiotherapy. Chemotherapy and radiotherapy have been ineffective for patients with inoperable tumours. For most of these patients biliary drainage is the mainstay of palliation. However, controversy exists over the type and positioning of biliary stents. Photodynamic treatment is a new palliative technique that might improve quality of life.
          Article 0 comments Cited 267 times – based on 0 reviews     Review now
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            A rapid in vitro assay for quantitating the invasive potential of tumor cells.

            A Albini, Y Iwamoto, H K Kleinman … (1987)
            We have reconstituted a matrix of basement membrane onto a filter in a Boyden chamber and assessed the ability of various malignant and nonmalignant cells to penetrate through the coated filter. Cells from all the malignant cell lines tested were able to cross the matrix in 5-6 h, whereas human fibroblasts as well as mouse 3T3 and 10T1/2 cell lines, which are not tumorigenic, were not invasive. In addition, normal primary prostate epithelial cells and benign prostatic hyperplasia cells were not invasive when tested in this assay, whereas malignant prostate carcinoma cells were highly invasive. Parallel experiments with these prostatic cells using the intrasplenic assay for metastasis detection in the nude mouse confirmed the benign behavior of the former cells and the metastatic phenotype of the latter ones. These results suggest that this in vitro test allows the rapid and quantitative assessment of invasiveness and a means to screen for drugs which alter the invasive phenotype of tumor cells.
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              Characterization of a side population of cancer cells from human gastrointestinal system.

              Tohru Utsunomiya, Koshi Mimori, Fumiaki Tanaka … (2006)
              A subset of stem cells, termed "side population" (SP) cells, has been identified and characterized in several mammalian tissues and cell lines. However, SP cells have never been identified or isolated from gastrointestinal cancers. We used flow cytometry and the DNA-binding dye Hoechst 33342 to isolate SP cells from various human gastrointestinal system cancer cell lines. Fifteen of sixteen cancer cell lines from the gastrointestinal system contained 0.3%-2.2% SP cells. Next, we used an oligonucleotide microarray to analyze differentially expressed genes between SP and non-SP cells of hepatoma HuH7. The expression of GATA6, which is associated with embryonic development and hepatocytic differentiation, was significantly upregulated in HuH7 SP cells. The expression of ABCG2, ABCB1, and CEACAM6, which are associated with chemoresistance, was also significantly increased in SP cells. In addition, some epithelial markers and mesenchymal markers were overexpressed in SP cells. Reverse transcription-polymerase chain reaction and immunocytochemical staining validated these results and suggested a multilineage potential for HuH7 SP cells. In hepatoma HuH7 and colorectal SW480 cell lines, SP cells showed evidence for self-renewal, generating both SP and non-SP cells. Finally, chemoresistance to anticancer agents, including doxorubicin, 5-fluorouracil, and gemcitabine, were compared between HuH7 SP and non-SP cells using an ATP bioluminescence assay. The HuH7 SP cells expressed a higher resistance to doxorubicin, 5-fluorouracil, and gemcitabine compared with non-SP cells. These findings demonstrate that cancers of the gastrointestinal system do contain SP cells that show some characteristics of so-called stem cells.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Br J Cancer
                Title: British Journal of Cancer
                ISSN (Print): 0007-0920
                ISSN (Electronic): 1532-1827
                Publication date (Electronic): 15 August 2006
                Publication date (Print): 21 August 2006
                Volume: 95
                Issue: 4
                Pages: 532-540
                Affiliations
                [1 ]Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University , 4546 Tsurumihara, Beppu, 874-0838, Japan
                [2 ]Department of General Surgical Science, Graduate School of Medicine, Gunma University , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
                Author notes
                [* ]Author for correspondence: mmori@ 123456beppu.kyushu-u.ac.jp
                Article
                Publisher Item ID: 6603276
                DOI: 10.1038/sj.bjc.6603276
                PMC ID: 2360665
                PubMed ID: 16868542
                SO-VID: 22c1acbb-7a30-4c8d-ad62-ccb2ecb58ba3
                Copyright © Copyright 2006, Cancer Research UK
                History
                Date received : 01 February 2006
                Date revision received : 02 June 2006
                Date accepted : 22 June 2006
                Categories
                Subject: Genetics and Genomics

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cholangiocarcinoma,carcinoembryonic antigen-related cell adhesion molecule 6 (ceacam6),gemcitabine
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cholangiocarcinoma, carcinoembryonic antigen-related cell adhesion molecule 6 (ceacam6), gemcitabine

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