1. ¹Department of Obstetric and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
2. ²Graduate Institute of Medical Informatics, Taipei Medical University, Taipei, Taiwan
3. ³National Institute of Cancer Research, National Health Research Institutes, Taipei, Taiwan
4. ⁴Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan
5. ⁵Mattel Children's Hospital, University of California at Los Angeles, Los Angeles, CA, USA
6. ⁶Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

Correspondence: Professor CT Lin, Department of Pathology, National Taiwan University Hospital and Institute of Pathology, National Taiwan University College of Medicine, No 7, Chung-Shan South Road, Taipei 10020, Taiwan. E-mail: ctl@ha.mc.ntu.edu.tw

Received 13 July 2007; Revised 6 September 2007; Accepted 17 September 2007; Published online 22 October 2007.

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.