TY - JOUR
T1 - Nanomolar EP4 receptor potency and expression of eicosanoid-related enzymes in normal appearing colonic mucosa from patients with colorectal neoplasia
AU - Feddersen, Ulrike Ries
AU - Hendel, Sebastian Kjærgaard
AU - Berner-Hansen, Mark Alexander
AU - Jepps, Thomas Andrew
AU - Berner-Hansen, Mark
AU - Bindslev, Niels
N1 - © 2022. The Author(s).
Correction to: BMC Gastroenterology (2022) 22:234 https://doi.org/10.1186/s12876-022-02311-z
After publication of this article [1], the authors reported that the last sentence of the Conclusions section “The observed aberrant gene expressions,” should have read: “The observed aberrant gene expressions, as an individual predisposition for early tumorigenesis, is still an open question.”
The original article [1] has been updated.
PY - 2022/5/12
Y1 - 2022/5/12
N2 - BACKGROUND: Aberrations in cyclooxygenase and lipoxygenase (LOX) pathways in non-neoplastic, normal appearing mucosa from patients with colorectal neoplasia (CRN), could hypothetically qualify as predisposing CRN-markers.METHODS: To test this hypothesis, biopsies were obtained during colonoscopy from macroscopically normal colonic mucosa from patients with and without CRN. Prostaglandin E2 (PGE2) receptors, EP1-4, were examined in Ussing-chambers by exposing biopsies to selective EP receptor agonists, antagonists and PGE2. Furthermore, mRNA expression of EP receptors, prostanoid synthases and LOX enzymes were evaluated with qPCR.RESULTS: Data suggest that PGE2 binds to both high and low affinity EP receptors. In particular, PGE2 demonstrated EP4 receptor potency in the low nanomolar range. Similar results were detected using EP2 and EP4 agonists. In CRN patients, mRNA-levels were higher for EP1 and EP2 receptors and for enzymes prostaglandin-I synthase, 5-LOX, 12-LOX and 15-LOX.CONCLUSIONS: In conclusion, normal appearing colonic mucosa from CRN patients demonstrates deviating expression in eicosanoid pathways, which might indicate a likely predisposition for early CRN development and furthermore that PGE2 potently activates high affinity EP4 receptor subtypes, supporting relevance of testing EP4 antagonists in colorectal neoplasia management.
AB - BACKGROUND: Aberrations in cyclooxygenase and lipoxygenase (LOX) pathways in non-neoplastic, normal appearing mucosa from patients with colorectal neoplasia (CRN), could hypothetically qualify as predisposing CRN-markers.METHODS: To test this hypothesis, biopsies were obtained during colonoscopy from macroscopically normal colonic mucosa from patients with and without CRN. Prostaglandin E2 (PGE2) receptors, EP1-4, were examined in Ussing-chambers by exposing biopsies to selective EP receptor agonists, antagonists and PGE2. Furthermore, mRNA expression of EP receptors, prostanoid synthases and LOX enzymes were evaluated with qPCR.RESULTS: Data suggest that PGE2 binds to both high and low affinity EP receptors. In particular, PGE2 demonstrated EP4 receptor potency in the low nanomolar range. Similar results were detected using EP2 and EP4 agonists. In CRN patients, mRNA-levels were higher for EP1 and EP2 receptors and for enzymes prostaglandin-I synthase, 5-LOX, 12-LOX and 15-LOX.CONCLUSIONS: In conclusion, normal appearing colonic mucosa from CRN patients demonstrates deviating expression in eicosanoid pathways, which might indicate a likely predisposition for early CRN development and furthermore that PGE2 potently activates high affinity EP4 receptor subtypes, supporting relevance of testing EP4 antagonists in colorectal neoplasia management.
KW - Colorectal cancer
KW - EP receptors
KW - Lipoxygenase
KW - Short circuit current
KW - mRNA expression
UR - https://www.scopus.com/pages/publications/85130637443
U2 - 10.1186/s12876-022-02311-z
DO - 10.1186/s12876-022-02311-z
M3 - Journal article
C2 - 35549670
SN - 1471-230X
VL - 22
SP - 234
JO - BMC Gastroenterology
JF - BMC Gastroenterology
IS - 1
M1 - 234
ER -