4.6 Article

Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines

Journal

PLOS ONE
Volume 16, Issue 3, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0248983

Keywords

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Funding

  1. National Health and Medical Research Council (NHMRC) of Australia [1083131, 1084083, 1143601, 1117017]
  2. Australian Research Council Centre of Excellence in Advanced Molecular Imaging [CE140100011]
  3. National Health and Medical Research Council of Australia [1084083, 1143601, 1083131] Funding Source: NHMRC

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The expression of PAR2 is decreased in renal cell carcinoma compared with normal kidney tissue, suggesting that PAR2 may not be a promising target for the treatment of this type of cancer.
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.

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