COX-2-dependent PGE₂ acts as a growth factor in mycosis fungoides (MF)

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 -