泌尿器科腫瘍学における分子研究の展望 : 発癌・転移機構(膀胱腫瘍)

Abstract

This report consists of a description of our research findings relating to the mechanism of cancer metastasis and target molecules for early diagnosis or cancer therapy. First, we investigated the significance of metastasis-related genes expressed to various extents in three human bladder cancer cell lines using two in vivo models. The relationship between the gene expression pattern and the behavior of cancer cells implicated a loss of E-cadherin expression as a critical factor in facilitating the progression of bladder cancer. Second, we examined the expression of human telomerase reverse transcriptase (hTERT) mRNA in voided urine samples in patients with bladder cancer. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed a higher positive rate as compared with cytological examination, suggesting that the expression of hTERT in urine samples may be a useful diagnostic marker for bladder cancer. Finally, we searched for a molecule to which antisense can be applied as a treatment modality. The 150 kDa oxygen regulated protein (ORP 150), a kind of heat shock proteins, functions as a molecular chaperone in the endoplasmic reticulum. We demonstrated that the adenoviral-mediated antisense ORP150 cDNA transfer resulted in the suppression of vascular endothelial growth factor (VEGF) expression and tumor growth in vivo. In addition, the significant correlation between ORP150 and matrix metalloproteinase 2 (MMP-2) expression was observed in bladder cancer, suggesting that ORP150 functions as a molecular chaperon to MMP-2 secretion for tumor invasion. Anti-sense ORP150 may therefore have a potentially stronger antitumor effect because of its multitargeting capability as a molecular chaperone.