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Title:
Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker | Molecular Cancer
Description:
Background Fibroblasts play important roles in several cancers. It was hypothesized that cholangiocarcinoma (CCA)-associated fibroblasts (Cfs) differ from non-tumorigenic liver fibroblasts (Lfs) in their gene expression profiles resulting in the capability to promote cancer. Periostin (PN) is a multi-functional protein and has emerged as a promising marker for tumor progression. The role of PN in CCA, however, has not yet been explored. Results In this study, the gene expression profile of Cfs in comparison to Lfs was performed using oligonucleotide microarrays. The common- and unique-expressed genes in Cfs and the promising roles in cancer promotion and progression were determined. PN was markedly over-expressed in Cfs confirmed by real time RT-PCR and western blot analysis. Immunohistochemistry examination of a number of patients with intrahepatic CCA showed the expression of PN solely in stromal fibroblasts, but was expressed neither in cancer cells nor immune cells. Low to no expression of PN was observed in tissues of benign liver disease and hepatocellular carcinoma. CCA patients with high levels of PN had significantly shorter survival time than those with low levels (P = 0.026). Multivariate analysis revealed high levels of PN (P = 0.045) and presence of lymph node metastasis (P = 0.002) as independent poor prognostic factors. The in vitro study revealed that recombinant PN induced CCA cell proliferation and invasion. Interestingly, interference RNA against integrin α5 significantly reduced the cellular response to PN-stimulated proliferation and invasion. Conclusion The gene expression profile of fibroblasts in CCA is apparently explored for the first time and has determined the genes involving in induction of this cancer progression. High PN can be used to distinguish CCA from other related liver diseases and is proposed as a prognostic factor of poor survival. Regulation of fibroblast-derived PN in CCA proliferation and invasion may be considered as an alternative therapeutic approach.
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Keywords {🔍}
cca, cancer, fibroblasts, cells, expression, cell, pubmed, article, google, scholar, cas, proliferation, genes, invasion, kkum, tissues, gene, liver, protein, fig, time, high, analysis, cfs, growth, results, survival, table, patients, showed, stromal, compared, lines, study, levels, itgα, periostin, performed, real, induce, authors, data, tumor, progression, full, thuwajit, carcinoma, human, size, figure,
Topics {✒️}
platelet-derived growth factor-aa α-smooth muscle actin benign liver tissue bile duct epithelial platelet-derived growth factor-α fibroblast-derived-pn-stimulated pathways hepatic stellate cells open access article o6-methylguanine-dna methyltransferase author information authors anti-rabbit igg-cy3 anti-mouse igg-alexa 488 mouse fibroblast nih-3t3 article download pdf real time rt-pcr fibroblast-derived proteins released combined hepatocellular carcinoma closely-related liver cancer peti thuwajit viverrini excretory/secretory product hypoxia-induced cell death csk-homologous kinase chk comparing gene profiles gene expression profile stromal-derived factor-1 secreted �chanitra thuwajit chanitra thuwajit author correspondence full size image parasitic product-treated fibroblasts pn-induced cell proliferation collagen-binding protein differing hepatocellular carcinoma showed scirrhous hepatocellular carcinoma poorly-differentiated malignant tissues full size table gene expression profiling human liver cancers normal fibroblast lines mitogen-activated protein kinase benign liver disease facilitate fibroblast proliferation cardiac fibroblast proliferation pn-induced-itgα5 pathway real time pcr colony formation assay de la chapelle excretory/secretory product epithelial ovarian carcinoma fibroblast-derived proteins
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headline:Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker
description:Fibroblasts play important roles in several cancers. It was hypothesized that cholangiocarcinoma (CCA)-associated fibroblasts (Cfs) differ from non-tumorigenic liver fibroblasts (Lfs) in their gene expression profiles resulting in the capability to promote cancer. Periostin (PN) is a multi-functional protein and has emerged as a promising marker for tumor progression. The role of PN in CCA, however, has not yet been explored. In this study, the gene expression profile of Cfs in comparison to Lfs was performed using oligonucleotide microarrays. The common- and unique-expressed genes in Cfs and the promising roles in cancer promotion and progression were determined. PN was markedly over-expressed in Cfs confirmed by real time RT-PCR and western blot analysis. Immunohistochemistry examination of a number of patients with intrahepatic CCA showed the expression of PN solely in stromal fibroblasts, but was expressed neither in cancer cells nor immune cells. Low to no expression of PN was observed in tissues of benign liver disease and hepatocellular carcinoma. CCA patients with high levels of PN had significantly shorter survival time than those with low levels (P = 0.026). Multivariate analysis revealed high levels of PN (P = 0.045) and presence of lymph node metastasis (P = 0.002) as independent poor prognostic factors. The in vitro study revealed that recombinant PN induced CCA cell proliferation and invasion. Interestingly, interference RNA against integrin α5 significantly reduced the cellular response to PN-stimulated proliferation and invasion. The gene expression profile of fibroblasts in CCA is apparently explored for the first time and has determined the genes involving in induction of this cancer progression. High PN can be used to distinguish CCA from other related liver diseases and is proposed as a prognostic factor of poor survival. Regulation of fibroblast-derived PN in CCA proliferation and invasion may be considered as an alternative therapeutic approach.
datePublished:2010-01-24T00:00:00Z
dateModified:2010-01-24T00:00:00Z
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keywords:
Stromal Fibroblast
AGN2
Human Basal Cell Carcinoma
Cancer Fibroblast
Benign Liver Tissue
Cancer Research
Oncology
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headline:Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker
description:Fibroblasts play important roles in several cancers. It was hypothesized that cholangiocarcinoma (CCA)-associated fibroblasts (Cfs) differ from non-tumorigenic liver fibroblasts (Lfs) in their gene expression profiles resulting in the capability to promote cancer. Periostin (PN) is a multi-functional protein and has emerged as a promising marker for tumor progression. The role of PN in CCA, however, has not yet been explored. In this study, the gene expression profile of Cfs in comparison to Lfs was performed using oligonucleotide microarrays. The common- and unique-expressed genes in Cfs and the promising roles in cancer promotion and progression were determined. PN was markedly over-expressed in Cfs confirmed by real time RT-PCR and western blot analysis. Immunohistochemistry examination of a number of patients with intrahepatic CCA showed the expression of PN solely in stromal fibroblasts, but was expressed neither in cancer cells nor immune cells. Low to no expression of PN was observed in tissues of benign liver disease and hepatocellular carcinoma. CCA patients with high levels of PN had significantly shorter survival time than those with low levels (P = 0.026). Multivariate analysis revealed high levels of PN (P = 0.045) and presence of lymph node metastasis (P = 0.002) as independent poor prognostic factors. The in vitro study revealed that recombinant PN induced CCA cell proliferation and invasion. Interestingly, interference RNA against integrin α5 significantly reduced the cellular response to PN-stimulated proliferation and invasion. The gene expression profile of fibroblasts in CCA is apparently explored for the first time and has determined the genes involving in induction of this cancer progression. High PN can be used to distinguish CCA from other related liver diseases and is proposed as a prognostic factor of poor survival. Regulation of fibroblast-derived PN in CCA proliferation and invasion may be considered as an alternative therapeutic approach.
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Stromal Fibroblast
AGN2
Human Basal Cell Carcinoma
Cancer Fibroblast
Benign Liver Tissue
Cancer Research
Oncology
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