Introduction of insulin-like growth factor binding protein-2 gene into human bladder cancer cells enhances their metastatic potential.

Abstract

Overexpression of insulin-like growth factor binding protein-2 (IGFBP-2) has been shown to be associated with tumor progression in several human malignant tumors; however, the significance of IGFBP-2 expression in bladder cancer remains poorly defined. The objective of this study was to investigate the effect of IGFBP-2 overexpression in human bladder cancer KoTCC-1 cells on their phenotype associated with tumor progression. We introduced IGFBP-2 cDNA into KoTCC-1 cells, which do not express a detectable level of IGFBP-2 protein, thus generating an IGFBP-2 overexpressing cell line (KoTCC-1/BP2). We also generated a vector-only-transfected cell line (KoTCC-1/C) as a control. Despite the absence of a significant difference in in vitro cell growth rates and motilities among KoTCC-1 sublines, KoTCC-1/BP2 exhibited significantly higher invasive ability than KoTCC-1/C. Gelatin zymography showed a marked increase in matrix metalloproteinase-2 (MMP-2) production by KoTCC-1/BP2 compared with that by KoTCC-1/C. Furthermore, there was no significant difference in sub-cutaneous tumor growth among KoTCC-1 sublines; however, more advanced tumor progression, including lymph node metastasis and hemorrhagic ascites formation, was observed after the implantation of KoTCC-1/BP2 into the bladder wall of nude mice than after the implantation of KoTCC-1/C. These findings suggest that overexpression of IGFBP-2 induces an increase in MMP-2 production, resulting in the enhanced metastatic potential of bladder cancer.

• Authors: Hideaki Miyake, Isao Hara, Kazuki Yamanaka, Mototsugu Muramaki, Martin Gleave, Hiroshi Eto
• Journal: Oncology reports (Oncol Rep) Vol. 13 Issue 2 Pg. 341-5 (Feb 2005) ISSN: 1021-335X [Print] Greece
• PMID: 15643522 (Publication Type: Journal Article)

Chemical References

• Insulin-Like Growth Factor Binding Protein 2
• Matrix Metalloproteinase 2

Topics

• Animals
• Cell Proliferation
• Female
• Humans
• Insulin-Like Growth Factor Binding Protein 2 (genetics)
• Lymphatic Metastasis
• Matrix Metalloproteinase 2 (metabolism)
• Mice
• Mice, Nude
• Neoplasm Invasiveness (genetics)
• Neoplasm Metastasis
• Neoplasm Transplantation
• Transfection
• Transplantation, Heterologous
• Tumor Cells, Cultured
• Urinary Bladder Neoplasms (genetics, pathology)