TY - JOUR
T1 - COX-2-dependent PGE2 acts as a growth factor in mycosis fungoides (MF)
AU - Kopp, Katharina Luise Maria
AU - Kauczok, C. S.
AU - Lauenborg, Britt Thyssing
AU - Krejsgaard, Thorbjørn Frej
AU - Eriksen, Karsten Wessel Kam
AU - Zhang, Q.
AU - Wasik, M. A.
AU - Geisler, Carsten
AU - Ralfkiaer, Elisabeth Methner
AU - Becker, J. C.
AU - Ødum, Niels
AU - Andersen, Anders Woetmann
PY - 2010/6
Y1 - 2010/6
N2 - Cancer often originates from a site of persistent inflammation, and the mechanisms turning chronic inflammation into a driving force of carcinogenesis are intensely investigated. Cyclooxygenase-2 (COX-2) is an inducible key modulator of inflammation that carries out the rate-limiting step in prostaglandin synthesis. Aberrant COX-2 expression and prostaglandin E 2 (PGE2) production have been implicated in tumorigenesis. In this study we show that COX-2 is ectopically expressed in malignant T-cell lines from patients with cutaneous T-cell lymphoma (CTCL) as well as in situ in lymphocytic cells in 21 out of 22 patients suffering from mycosis fungoides (MF) in plaque or tumor stage. COX-2 is not expressed in lymphocytes of 11 patients with patch-stage MF, whereas sporadic COX-2 staining of stromal cells is observed in the majority of patients. COX-2 expression correlates with a constitutive production of PGE2 in malignant T cells in vitro. These cells express prostaglandin receptors EP3 and EP4 and the receptor antagonist as well as small interfering RNA (siRNA) directed against COX-2, and specific COX-2 inhibitors strongly reduce their spontaneous proliferation. In conclusion, our data indicate that COX-2 mediated PGE2 exerts an effect as a tumor growth factor in MF.
AB - Cancer often originates from a site of persistent inflammation, and the mechanisms turning chronic inflammation into a driving force of carcinogenesis are intensely investigated. Cyclooxygenase-2 (COX-2) is an inducible key modulator of inflammation that carries out the rate-limiting step in prostaglandin synthesis. Aberrant COX-2 expression and prostaglandin E 2 (PGE2) production have been implicated in tumorigenesis. In this study we show that COX-2 is ectopically expressed in malignant T-cell lines from patients with cutaneous T-cell lymphoma (CTCL) as well as in situ in lymphocytic cells in 21 out of 22 patients suffering from mycosis fungoides (MF) in plaque or tumor stage. COX-2 is not expressed in lymphocytes of 11 patients with patch-stage MF, whereas sporadic COX-2 staining of stromal cells is observed in the majority of patients. COX-2 expression correlates with a constitutive production of PGE2 in malignant T cells in vitro. These cells express prostaglandin receptors EP3 and EP4 and the receptor antagonist as well as small interfering RNA (siRNA) directed against COX-2, and specific COX-2 inhibitors strongly reduce their spontaneous proliferation. In conclusion, our data indicate that COX-2 mediated PGE2 exerts an effect as a tumor growth factor in MF.
U2 - 10.1038/leu.2010.66
DO - 10.1038/leu.2010.66
M3 - Journal article
C2 - 20428208
SN - 0887-6924
VL - 24
SP - 1179
EP - 1185
JO - Leukemia
JF - Leukemia
IS - 6
ER -
