Bladder cancer. Human leukocyte antigen II, interleukin-6, and interleukin-6 receptor expression determined by the polymerase chain reaction

Abstract

The prediction of tumour biology rarely rests upon a single characteristic of the malignancy. The analysis of a single gene can complement standard histologic evaluation. The investigation of new parameters as well as the routine clinical analysis of gene expression is often limited because of the small amount of tissue available. This is particularly true of de novo human bladder cancers because they are generally small or handled in such a way as to hinder the analysis of multiple different parameters. Analysis of expressed mRNA by the polymerase chain reaction (RNA/PCR) is a method that allows the development of a profile of bladder cancer gene expression. The authors report the use of the RNA/PCR method to examine in bladder cancer the expression of the human leukocyte antigen (HLA) class II gene family (HLA-DR, DQ, and DP) as well as interleukin-6 (IL-6) and the interleukin-6 receptor (IL-6R). All de novo transitional cell carcinomas, one squamous carcinoma, and two transitional cell carcinoma cell lines expressed the majority of HLA class II genes. All samples expressed IL-6R RNA whereas production of IL-6 message was limited to one of the cell lines and to the high-grade bladder cancers. These results were combined with stage, grade, and DNA content to develop a profile of the cancers examined. Although an improved predictive index based on gene expression analysis by RNA/PCR has not been realized, a broader survey of human tumors for expression of these genes and others is likely to refine the classification of bladder cancer.

A Novel TLR4-Mediated Signaling Pathway Leading to IL-6 Responses in Human Bladder Epithelial Cells

“…One of the primary cell types in the urinary tract reacting to BEC-generated IL-6 are also BECs. These cells possess IL-6 receptors [54] and this cytokine, acting in autocrine fashion, may trigger various antimicrobial responses, such as production of antimicrobial peptides [55] and mucins, [56] as well as promote exfoliation of infected BECs.…”

Expression of Markers for Transitional Cell Carcinoma in Normal Bladder Mucosa of Patients with Bladder Cancer

“…22 Only scant data on the relation between HLA-II ex pression and bladder cancer have been published and al though HLA-II expression was found in bladder cancer and correlated with B C G therapy23,24 and was induced by cyto kines,25 no correlation has been found between HLA-II ex pression and tumor aggressiveness. 24,26 A consistent value of the epidermal growth factor receptor (EGF-R) in T C C has been recently reported.9-27 Normally, EGF-R is found only on the basal layer of epithelial cells. In bladder tumors the urinary concentration of E G F can be decreased, but EGF-R expression in tumors is higher than in normal urothelium.…”

Translating IL-6 biology into effective treatments

“…Both signalling routes involve phosphorylation of Janus kinase 1 (JAK1), JAK2 and tyrosine kinase 2 (TYK2), which can also be targeted therapeutically with different molecules but are not the focus of this article 4 . The decision to target IL-6R rather than IL-6 itself was made, taking into consideration that concentrations of the receptor have less interpatient variability than concentrations of IL-6, potentially simplifying dose and regimen selection 8,9 . With concurrent advances in biotechnology, the two groups decided to develop a humanized monoclonal antibody targeting IL-6R [10][11][12] .…”