Introduction of insulin-like growth factor binding protein-2 gene into human bladder cancer cells enhances their metastatic potential.
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.
Miyake
Hideaki
H
Department of Urology, Hyogo Medical Center for Adults, 13-70 Kitaohji-cho, Akashi 673-8558, Japan. hideakimiyake@hotmail.com
Hara
Isao
I
Yamanaka
Kazuki
K
Muramaki
Mototsugu
M
Gleave
Martin
M
Eto
Hiroshi
H
D000818:Animals; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics*; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D018971:Insulin-Like Growth Factor Binding Protein 2; D020778:Matrix Metalloproteinase 2