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High PGD2 receptor 2 levels are associated with poor prognosis in colorectal cancer patients and induce VEGF expression in colon cancer cells and migration in a zebrafish xenograft model

Dash, Pujarini LU ; Ghatak, Souvik LU ; Topi, Geriolda LU ; Satapathy, Shakti Ranjan LU ; Ek, Fredrik LU ; Hellman, Karin LU ; Olsson, Roger LU orcid ; Mehdawi, Lubna M. LU and Sjölander, Anita LU (2022) In British Journal of Cancer 126(4). p.586-597
Abstract

Background: Despite intense research, the prognosis for patients with advanced colorectal cancer (CRC) remains poor. The prostaglandin D2 receptors DP1 and DP2 are explored here as potential therapeutic targets for advanced CRC. Methods: A CRC cohort was analysed to determine whether DP1 and DP2 receptor expression correlates with patient survival. Four colon cancer cell lines and a zebrafish metastasis model were used to explore how DP1/DP2 receptor expression correlates with CRC progression. Results: Analysis of the clinical CRC cohort revealed high DP2 expression in tumour tissue, whereas DP1 expression was low. High DP2 expression negatively correlated with overall survival. Other pathological indicators, such as TNM... (More)

Background: Despite intense research, the prognosis for patients with advanced colorectal cancer (CRC) remains poor. The prostaglandin D2 receptors DP1 and DP2 are explored here as potential therapeutic targets for advanced CRC. Methods: A CRC cohort was analysed to determine whether DP1 and DP2 receptor expression correlates with patient survival. Four colon cancer cell lines and a zebrafish metastasis model were used to explore how DP1/DP2 receptor expression correlates with CRC progression. Results: Analysis of the clinical CRC cohort revealed high DP2 expression in tumour tissue, whereas DP1 expression was low. High DP2 expression negatively correlated with overall survival. Other pathological indicators, such as TNM stage and metastasis, positively correlated with DP2 but not DP1 expression. In accordance, the in vitro results showed high DP2 expression in four CC-cell lines, but only one expressed DP1. DP2 stimulation resulted in increased proliferation, p-ERK1/2 and VEGF expression/secretion. DP2-stimulated cells exhibited increased migration in the zebrafish metastasis model. Conclusion: Our results support DP2 receptor expression and signalling as a therapeutic target in CRC progression based on its expression in CRC tissue correlating with poor patient survival and that it triggers proliferation, p-ERK1/2 and VEGF expression and release and increased metastatic activity in CC-cells.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
126
issue
4
pages
586 - 597
publisher
Nature Publishing Group
external identifiers
  • pmid:34750492
  • scopus:85118644224
ISSN
0007-0920
DOI
10.1038/s41416-021-01595-4
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
id
f3c5c93f-0727-4ddc-a67c-3c8674392c53
date added to LUP
2021-11-29 11:40:32
date last changed
2024-07-14 00:07:49
@article{f3c5c93f-0727-4ddc-a67c-3c8674392c53,
  abstract     = {{<p>Background: Despite intense research, the prognosis for patients with advanced colorectal cancer (CRC) remains poor. The prostaglandin D<sub>2</sub> receptors DP1 and DP2 are explored here as potential therapeutic targets for advanced CRC. Methods: A CRC cohort was analysed to determine whether DP1 and DP2 receptor expression correlates with patient survival. Four colon cancer cell lines and a zebrafish metastasis model were used to explore how DP1/DP2 receptor expression correlates with CRC progression. Results: Analysis of the clinical CRC cohort revealed high DP2 expression in tumour tissue, whereas DP1 expression was low. High DP2 expression negatively correlated with overall survival. Other pathological indicators, such as TNM stage and metastasis, positively correlated with DP2 but not DP1 expression. In accordance, the in vitro results showed high DP2 expression in four CC-cell lines, but only one expressed DP1. DP2 stimulation resulted in increased proliferation, p-ERK1/2 and VEGF expression/secretion. DP2-stimulated cells exhibited increased migration in the zebrafish metastasis model. Conclusion: Our results support DP2 receptor expression and signalling as a therapeutic target in CRC progression based on its expression in CRC tissue correlating with poor patient survival and that it triggers proliferation, p-ERK1/2 and VEGF expression and release and increased metastatic activity in CC-cells.</p>}},
  author       = {{Dash, Pujarini and Ghatak, Souvik and Topi, Geriolda and Satapathy, Shakti Ranjan and Ek, Fredrik and Hellman, Karin and Olsson, Roger and Mehdawi, Lubna M. and Sjölander, Anita}},
  issn         = {{0007-0920}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{586--597}},
  publisher    = {{Nature Publishing Group}},
  series       = {{British Journal of Cancer}},
  title        = {{High PGD<sub>2</sub> receptor 2 levels are associated with poor prognosis in colorectal cancer patients and induce VEGF expression in colon cancer cells and migration in a zebrafish xenograft model}},
  url          = {{http://dx.doi.org/10.1038/s41416-021-01595-4}},
  doi          = {{10.1038/s41416-021-01595-4}},
  volume       = {{126}},
  year         = {{2022}},
}