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An increased expression of cysteinyl leukotriene 2 receptor in colorectal adenocarcinomas correlates with high differentiation

Magnusson, Cecilia LU ; Ehrnström, Roy LU ; Olsen, Jorgen and Sjölander, Anita LU (2007) In Cancer Research 67(19). p.9190-9198
Abstract
Increased levels of inflammatory mediators such as cystenyl leukotrienes (CysLT) have been found in and around tumors. These data, along with our previous observation that the G-protein-coupled receptor CysLT(1)R, which signals survival and proliferation, is up-regulated in colon cancer, suggest an important role for CysLT(1)R in tumor development. The objective of this study was to examine the expression and function of the low-affinity CysLT(2) receptor (CysLT(2)R) in colon cancer. We found lower expression levels of CysLT(2)R compared with CysLT(1)R in cancer cell lines as well as clinical tumor material. Interestingly, CysLT(2)R, like CysLT(1)R, was found to be one of few G-protein-coupled receptors that are located both at the plasma... (More)
Increased levels of inflammatory mediators such as cystenyl leukotrienes (CysLT) have been found in and around tumors. These data, along with our previous observation that the G-protein-coupled receptor CysLT(1)R, which signals survival and proliferation, is up-regulated in colon cancer, suggest an important role for CysLT(1)R in tumor development. The objective of this study was to examine the expression and function of the low-affinity CysLT(2) receptor (CysLT(2)R) in colon cancer. We found lower expression levels of CysLT(2)R compared with CysLT(1)R in cancer cell lines as well as clinical tumor material. Interestingly, CysLT(2)R, like CysLT(1)R, was found to be one of few G-protein-coupled receptors that are located both at the plasma membrane and the nuclear membrane. No effect of CysLT(2)R signaling on cell proliferation was observed, nor was there a correlation between CysLT2R and different proliferation markers such as KI-67 and cyclooxygenase-2 in the tumor material. Instead, we found that activation of this receptor in colon cancer cells led to cellular differentiation similar to the effects of butyrate treatment. In accordance with this finding, we found that reduced expression of CysLT(2)R in colon cancer was associated with poor prognosis. We report the novel finding that CysLT(2)R signaling leads to terminal differentiation of colon carcinoma cells and growth inhibition, and that its expression is relatively high in less malignant forms of colon cancer. These data suggest that the balance between these two receptors is important for tumor progression and disease outcome. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Caco-2 Cells, Cell Differentiation: physiology, Apoptosis: physiology, Leukotriene: biosynthesis, Receptors, Adenocarcinoma: metabolism, Adenocarcinoma: pathology, Cell Growth Processes: physiology, Colorectal Neoplasms: metabolism, G0 Phase: physiology, Colorectal Neoplasms: pathology, Leukotriene: metabolism, Membrane Proteins: metabolism, Membrane Proteins: biosynthesis, Humans
in
Cancer Research
volume
67
issue
19
pages
9190 - 9198
publisher
American Association for Cancer Research Inc.
external identifiers
  • wos:000249955500030
  • scopus:35148834706
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-07-0771
language
English
LU publication?
yes
id
cc872e19-3c91-41d3-84a0-a83a2d703f64 (old id 656192)
date added to LUP
2007-12-13 11:48:49
date last changed
2017-04-09 04:13:39
@article{cc872e19-3c91-41d3-84a0-a83a2d703f64,
  abstract     = {Increased levels of inflammatory mediators such as cystenyl leukotrienes (CysLT) have been found in and around tumors. These data, along with our previous observation that the G-protein-coupled receptor CysLT(1)R, which signals survival and proliferation, is up-regulated in colon cancer, suggest an important role for CysLT(1)R in tumor development. The objective of this study was to examine the expression and function of the low-affinity CysLT(2) receptor (CysLT(2)R) in colon cancer. We found lower expression levels of CysLT(2)R compared with CysLT(1)R in cancer cell lines as well as clinical tumor material. Interestingly, CysLT(2)R, like CysLT(1)R, was found to be one of few G-protein-coupled receptors that are located both at the plasma membrane and the nuclear membrane. No effect of CysLT(2)R signaling on cell proliferation was observed, nor was there a correlation between CysLT2R and different proliferation markers such as KI-67 and cyclooxygenase-2 in the tumor material. Instead, we found that activation of this receptor in colon cancer cells led to cellular differentiation similar to the effects of butyrate treatment. In accordance with this finding, we found that reduced expression of CysLT(2)R in colon cancer was associated with poor prognosis. We report the novel finding that CysLT(2)R signaling leads to terminal differentiation of colon carcinoma cells and growth inhibition, and that its expression is relatively high in less malignant forms of colon cancer. These data suggest that the balance between these two receptors is important for tumor progression and disease outcome.},
  author       = {Magnusson, Cecilia and Ehrnström, Roy and Olsen, Jorgen and Sjölander, Anita},
  issn         = {1538-7445},
  keyword      = {Caco-2 Cells,Cell Differentiation: physiology,Apoptosis: physiology,Leukotriene: biosynthesis,Receptors,Adenocarcinoma: metabolism,Adenocarcinoma: pathology,Cell Growth Processes: physiology,Colorectal Neoplasms: metabolism,G0 Phase: physiology,Colorectal Neoplasms: pathology,Leukotriene: metabolism,Membrane Proteins: metabolism,Membrane Proteins: biosynthesis,Humans},
  language     = {eng},
  number       = {19},
  pages        = {9190--9198},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {An increased expression of cysteinyl leukotriene 2 receptor in colorectal adenocarcinomas correlates with high differentiation},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-07-0771},
  volume       = {67},
  year         = {2007},
}