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

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 ca...

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Main Authors: Morais, Christudas, Rajandram, Retnagowri, Blakeney, Jade S., Iyer, Abishek, Suen, Jacky Y., Johnson, David W., Gobe, Glenda C., Fairlie, David P., Vesey, David A.
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Published: PUBLIC LIBRARY SCIENCE
Online Access:http://eprints.um.edu.my/34231/
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spelling my.um.eprints.342312022-07-19T02:01:50Z http://eprints.um.edu.my/34231/ Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines Morais, Christudas Rajandram, Retnagowri Blakeney, Jade S. Iyer, Abishek Suen, Jacky Y. Johnson, David W. Gobe, Glenda C. Fairlie, David P. Vesey, David A. 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. PUBLIC LIBRARY SCIENCE Article NonPeerReviewed Morais, Christudas and Rajandram, Retnagowri and Blakeney, Jade S. and Iyer, Abishek and Suen, Jacky Y. and Johnson, David W. and Gobe, Glenda C. and Fairlie, David P. and Vesey, David A. Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines. PLOS ONE, 16 (3).
institution Universiti Malaya
building UM Library
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description 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.
format Article
author Morais, Christudas
Rajandram, Retnagowri
Blakeney, Jade S.
Iyer, Abishek
Suen, Jacky Y.
Johnson, David W.
Gobe, Glenda C.
Fairlie, David P.
Vesey, David A.
spellingShingle Morais, Christudas
Rajandram, Retnagowri
Blakeney, Jade S.
Iyer, Abishek
Suen, Jacky Y.
Johnson, David W.
Gobe, Glenda C.
Fairlie, David P.
Vesey, David A.
Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines
author_facet Morais, Christudas
Rajandram, Retnagowri
Blakeney, Jade S.
Iyer, Abishek
Suen, Jacky Y.
Johnson, David W.
Gobe, Glenda C.
Fairlie, David P.
Vesey, David A.
author_sort Morais, Christudas
title Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines
title_short Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines
title_full Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines
title_fullStr Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines
title_full_unstemmed Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines
title_sort expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines
publisher PUBLIC LIBRARY SCIENCE
url http://eprints.um.edu.my/34231/
_version_ 1739828488712486912
score 13.211869

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