Abstract
Expression of the protease sensing receptor, protease activated receptor-2 (PAR2), is elevated in a variety of cancers and has been promoted as a potential therapeutic target. With the development of potent antagonists for this receptor, we hypothesised that they could be used to treat renal cell carcinoma (RCC). The expression of PAR2 was, therefore, examined in human RCC tissues and selected RCC cell lines. Histologically confirmed cases of RCC, together with paired non-involved kidney tissue, were used to produce a tissue microarray (TMA) and to extract total tissue RNA. Immunohistochemistry and qPCR were then used to assess PAR2 expression. In culture, RCC cell lines versus primary human kidney tubular epithelial cells (HTEC) were used to assess PAR2 expression by qPCR, immunocytochemistry and an intracellular calcium mobilization assay. The TMA revealed an 85% decrease in PAR2 expression in tumour tissue compared with normal kidney tissue. Likewise, qPCR showed a striking reduction in PAR2 mRNA in RCC compared with normal kidney. All RCC cell lines showed lower levels of PAR2 expression than HTEC. In conclusion, we found that PAR2 was reduced in RCC compared with normal kidney and is unlikely to be a target of interest in the treatment of this type of cancer.
Highlights
Renal cell carcinoma (RCC) accounts for about 3% of adult malignancies [1, 2]
They reported that activation of the PI3K/AKT pathway was central to promoting the invasion and migration of RCC cells
RT-PCR and immunohistochemistry assays showed that protease activated receptor-2 (PAR2) expression was significantly increased in human RCC tissue compared with the adjacent non-neoplastic kidney tissue
Summary
Renal cell carcinoma (RCC) accounts for about 3% of adult malignancies [1, 2]. Together with the highly drug-resistant nature of this cancer, and the fact that diagnosis usually occurs at advanced stages due to lack of early warning signs, understanding the molecular pathogenesis of RCC and refining diagnostic and treatment options are of great importance [3]. The modification of extracellular matrix components by extracellular proteases plays a critical role in tumour progression, invasion and metastasis [4,5,6,7,8,9,10,11,12,13].
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