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Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma

Oncogene volume 27, pages 2137–2147 (2008)Cite this article

Abstract

Metastasis and invasion occur in the majority of epithelial ovarian carcinoma at diagnosis. To delineate the molecular signature in ovarian cancer invasion, we established and characterized a human ovarian endometrioid carcinoma (EC) cell line OVTW59-P0 and its invasion-related sublines (P1–P4, in the order of increasing invasive activity). P4 showed faster migration and larger xenograft formation with metastasis than P0. By microarray analysis of different gene expression among P0–P4 sublines, one group of gene was found negatively correlated with cancer invasion. Among these genes, IGFBP-3 was identified as one of the most remarkably suppressed gene that showed lower gene expression in P4 than P0. Re-expression of IGFBP-3 in P4 effectively inhibited cell migration, invasion and metastasis, but did not affect cell proliferation. In 35 patients with EC tumors, low IGFBP-3 expression correlated clinically with higher tumor grade, advanced stage and poor survival. Our results provide evidence and indicate that IGFBP-3 plays an important role as an invasion-metastasis suppressor in ovarian EC.

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Acknowledgements

We thank Dr Tsui-Lien Mao from the Department of Pathology for pathological diagnosis, Miss Li-Shu Chang from the Department of Medical Genetics for karyotypic analysis and Dr Chee-Jen Chan from the Department of Medical Research for consultation in statistic analysis. We also thank Dr Wen-Hwa Lee from the University of California at Irvine for his helpful discussion. This work was supported partly by National Science Council (NSC94-2314-B-002-208), National Health Research Institutes (NHRI-EX94-9416B1, NHRI-EX95-9416B1) and National Taiwan University Hospital (NTUH92-S057).

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Authors and Affiliations

  1. Department of Obstetric and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    P-L Torng & S-C Huang

  2. Graduate Institute of Medical Informatics, Taipei Medical University, Taipei, Taiwan

    Y-Cg Lee

  3. National Institute of Cancer Research, National Health Research Institutes, Taipei, Taiwan

    C-Yf Huang, Y-S Lin, Y-W Chu & C-W Wu

  4. Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan

    J-H Ye & C-T Lin

  5. Mattel Children's Hospital, University of California at Los Angeles, Los Angeles, CA, USA

    P Cohen

  6. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

    C-T Lin

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  1. P-L Torng
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Correspondence to C-T Lin.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Torng, PL., Lee, YC., Huang, CY. et al. Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma. Oncogene 27, 2137–2147 (2008). https://doi.org/10.1038/sj.onc.1210864

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