Lack of Decorin Expression by Human Bladder Cancer Cells Offers New Tools in the Therapy of Urothelial Malignancies

Abstract

Decorin, a multifunctional small leucine-rich extracellular matrix proteoglycan, has been shown to possess potent antitumour activity. However, there is some uncertainty whether different cancer cells express decorin in addition to non-malignant stromal cells. In this study we clarified decorin expression by human bladder cancer cells both in vivo and in vitro. In addition, the effect of adenovirus-mediated decorin expression on human bladder cancer cells in vitro was examined. We first demonstrated using the publicly available GeneSapiens databank that decorin gene expression is present in both normal and malignant human bladder tissues. However, when we applied in situ hybridization with digoxigenin-labeled RNA probes for decorin on human bladder carcinoma tissue samples derived from a large radical cystectomy patient cohort (n = 199), we unambiguously demonstrated that invasive and non-invasive bladder carcinoma cells completely lack decorin mRNA. The cancer cells were also negative for decorin immunoreactivity. Instead, decorin expression was localized solely to original non-malignant stromal areas of bladder tissue. In accordance with the aforementioned results, human bladder cancer cells in vitro were also negative for decorin expression as shown by RT-qPCR analyses. The lack of decorin expression by bladder cancer cells was shown not to be due to the methylation of the proximal promoter region of the decorin gene. When bladder cancer cells were transfected with a decorin adenoviral vector, their proliferation was significantly decreased. In conclusion, we have shown that human bladder cancer cells are totally devoid of decorin expression. We have also shown that adenovirus-mediated decorin gene transduction of human bladder cancer cell lines markedly inhibits their proliferation. Thus, decorin gene delivery offers new potential therapeutic tools in urothelial malignancies.

Decorin‐mediated oncosuppression – a potential future adjuvant therapy for human epithelial cancers

“…Indeed, the progression of cancer is known to be dependent on the complex interactions between cancer cells and their adjacent stromal cells (Theocharis and Karamanos, ). Regarding carcinomas, the malignant cells completely lack decorin expression (Boström et al, ; Nyman et al, ; Sainio et al, ). However, decorin can be produced by the peritumoral stromal cells, for example, cancer‐associated fibroblasts.…”

“…Originally, this was observed when mice lacking both decorin and p53 were shown to exhibit a faster rate of tumour growth than p53 null animals, suggesting that the lack of decorin was tumour‐permissive (Iozzo et al, ). Today, we know that in different malignancies such as breast cancer, bladder cancer and colon cancer, the expression of decorin is markedly decreased (Theocharis and Karamanos, ), so that the malignant cells of these carcinomas do not express decorin (Boström et al, ; Sainio et al, ; Nyman et al, ). On the other hand, the delivery of decorin or the induction of its expression in carcinoma cells has been shown to attenuate the malignant behaviour of cells through a variety of mechanisms (Bi and Yang, ; Neill et al, ; Boström et al, ).…”

Recombinant fibromodulin and decorin effects on NF-κB and TGFβ1 in the 4T1 breast cancer cell line

“…Expression of replication-defective adenovirus containing bovine Fmod cDNA (Rad-Fmod) and human Dcn cDNA (Rad-Dcn) were identified in the 4T1 breast cancer cell line using RT-PCR. The 4T1 breast cancer cell line is highly metastatic and was established to be negative for Fmod and Dcn transcripts (28,29). Following 4T1 cell line adenoviral infection, mRNA was extracted and RT-PCR using specific PCR primers was performed.…”

Decorin in Human Colon Cancer

“…Results from our previous studies have shown that decorin transduction into human breast cancer and bladder cancer cell lines leads to decreased proliferation of the cells Sainio et al 2013). Moreover, decorin transduction increases apoptosis in breast cancer cells ).…”