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01.12.2010 | Research | Ausgabe 1/2010 Open Access

Molecular Cancer 1/2010

Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker

Zeitschrift:
Molecular Cancer > Ausgabe 1/2010
Autoren:
Kusumawadee Utispan, Peti Thuwajit, Yoshimitsu Abiko, Komgrid Charngkaew, Anucha Paupairoj, Siri Chau-in, Chanitra Thuwajit
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-4598-9-13) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

KU performed most of the experiments and helped to draft the manuscript. YA contributed to the microarray experiment. PT performed real time PCR of some genes and helped KC and AP in immunohistochemical scoring. SC contributed to the patient clinicopathological data and samples collection. CT contributed to the design of the entire study, data analysis and preparation of the manuscript.
All authors have read and approved the final manuscript.

Abstract

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.
Zusatzmaterial
Authors’ original file for figure 1
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Authors’ original file for figure 7
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Authors’ original file for figure 8
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Literatur
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