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

Christudas Morais1,2, Retnagowri Rajandram3, Jade S Blakeney4

  • 1Centre for Kidney Disease Research, The University of Queensland, Translational Research Institute, Brisbane, Australia.

Plos One
|March 25, 2021
PubMed

Insights

Protease activated receptor-2 (PAR2) is reduced in renal cell carcinoma (RCC) tumors compared to normal kidney tissue. This finding suggests PAR2 is not a viable therapeutic target for treating this cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Protease activated receptor-2 (PAR2) is implicated in various cancers and considered a potential therapeutic target.
  • Antagonists for PAR2 have been developed, prompting investigation into their use for renal cell carcinoma (RCC).

Purpose of the Study:

  • To investigate the expression of PAR2 in human RCC tissues and cell lines.
  • To determine if PAR2 is a suitable therapeutic target for RCC treatment.

Main Methods:

  • Tissue microarray (TMA) construction from RCC and paired normal kidney tissues.
  • Quantitative polymerase chain reaction (qPCR) and immunohistochemistry to assess PAR2 expression.
  • Analysis of PAR2 expression in RCC cell lines and primary human kidney tubular epithelial cells (HTEC) using qPCR, immunocytochemistry, and intracellular calcium mobilization assays.

Main Results:

  • TMA analysis showed an 85% decrease in PAR2 expression in RCC tissue compared to normal kidney tissue.
  • qPCR revealed a significant reduction in PAR2 mRNA levels in RCC compared to normal kidney samples.
  • All examined RCC cell lines exhibited lower PAR2 expression levels than HTEC.

Conclusions:

  • PAR2 expression is significantly reduced in RCC compared to normal kidney tissue.
  • The downregulation of PAR2 in RCC suggests it is unlikely to be an effective therapeutic target for this cancer.