Bladder cancer cell invasion is enhanced by cross-talk with fibroblasts through hepatocyte growth factor.
OBJECTIVE
To examine the effects of fibroblast-derived humoral factors, especially hepatocyte growth factor (HGF), on the invasive potential of bladder cancer cells. Stromal cells in cancer tissue are thought to play an important role in the transformation and invasion of cancer cells.


METHODS
The influence of fibroblast cells (TIG-1 cells) and HGF on the invasive potential of bladder cancer cells (5637, T24, J82, HT1376, and MGHU-1 cells) was evaluated by in vitro cell invasion assay. The expression of HGF and c-Met, which is the receptor of HGF, was examined by reverse transcriptase-polymerase chain reaction. To clarify the relationship between the serum HGF level and invasive bladder cancer, we measured the serum concentrations of HGF in patients with bladder cancer without metastatic disease and normal controls, using an enzyme-linked immunosorbent assay.


RESULTS
The in vitro cell invasion assay showed that the number of invading bladder cancer cells was significantly increased by the conditioned medium (CM) of the fibroblast cells. HGF neutralization antibody partially inhibited the enhancement of invasiveness by fibroblast CM. The CM of fibroblasts cultured with bladder cancer CM stimulated cancer cell invasion more strongly (with increased HGF secretion) than did the CM of fibroblasts cultured without bladder cancer CM. The serum HGF levels were significantly greater in patients with muscle-invasive bladder cancer (regardless of tumor size) than in patients with non-muscle-invasive bladder cancer.


CONCLUSIONS
The present results have suggested that bladder cancer cell invasion is enhanced by cross-talk with fibroblasts through humoral factors, including HGF. Elucidation of this mechanism could lead to novel therapeutic strategies for bladder cancer.
Wang
Pengfei
P
Department of Urology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Nishitani
Masa-aki
MA
Tanimoto
Shuji
S
Kishimoto
Tomoteru
T
Fukumori
Tomoharu
T
Takahashi
Masayuki
M
Kanayama
Hiro-omi
HO
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002450:Cell Communication; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D017228:Hepatocyte Growth Factor