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

• Published in: Oncogene Vol. 27; no. 15; pp. 2137 - 2147
• Main Authors: Torng, P-L, Lee, Y-Cg, Huang, C-Yf, Ye, J-H, Lin, Y-S, Chu, Y-W, Huang, S-C, Cohen, P, Wu, C-W, Lin, C-T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-04-2008; Nature Publishing; Nature Publishing Group
• Subjects: Adult; Aged; Apoptosis; Binding proteins; Biological and medical sciences; Carcinoma, Endometrioid - diagnosis; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - mortality; Care and treatment; Cell Biology; Cell Culture Techniques; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell physiology; Cell proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cluster Analysis; Cytogenetic Analysis; Disease Progression; DNA microarrays; Endometrial cancer; Female; Female genital diseases; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Genetic aspects; Gynecology. Andrology. Obstetrics; Human Genetics; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3 - genetics; Insulin-Like Growth Factor Binding Protein 3 - physiology; Insulin-like growth factor-binding protein 3; Internal Medicine; Invasiveness; Medical sciences; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Molecular and cellular biology; Neoplasm Invasiveness; Neoplasm Metastasis; Oligonucleotide Array Sequence Analysis; Oncology; original-article; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Physiological aspects; Prognosis; Proteins; Risk factors; Survival Analysis; Tumor suppressor genes; Tumors; Xenografts; Taiwan; ovarian endometrioid carcinoma; invasion; insulin-like growth factor binding protein-3; suppressor; Ovary carcinoma; Malignant tumor; Metastasis; Carcinogenesis; Female genital diseases; Insulin like growth factor binding protein; Ovarian diseases; Endometrioid carcinoma; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210864

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.