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Blood, 1 August 2001, Vol. 98, No. 3, pp. 762-770
NEOPLASIA
STAT3 is constitutively activated in Hodgkin
cell lines
Dieter Kube,
Udo Holtick,
Martina Vockerodt,
Tahamtan Ahmadi,
Birgit Haier,
Iris Behrmann,
Peter C. Heinrich,
Volker Diehl, and
Hans Tesch
From Klinik für Innere Medizin I, Zentrum
für Molekulare Medizin der Universität Köln, Germany;
Institut für Biochemie RWTH-Klinikum Aachen, Germany; and
Eberhard-Karls-Universität Tübingen, Institut für
Tropenmedizin, Sektion für Humanparasitologie, Germany.
Hodgkin disease (HD) represents a malignant lymphoma in which the
putative malignant Hodgkin and Reed-Sternberg cells are rare and
surrounded by abundant reactive nonmalignant cells. It has been
suggested that cytokines such as interleukin-6 (IL-6) are involved in
the pathogenesis of the disease. The expression of the IL-6 receptor
(IL-6R) complex and its link to the activation of signal transducers
and activators of transcription (STAT) molecules in HD cell lines was
investigated. Gel retardation and Western blot analyses revealed a high
level of constitutively activated STAT3 in 5 of 7 HD cell lines, which
could not be detected in Burkitt lymphoma cell lines. Different levels
of IL-6R protein were measured in various HD cell lines: L428 and Dev
cells were characterized by very low levels of gp80 and gp130, on KMH2
cells only gp130 but no gp80 was detected, whereas L540, L591, HDLM2, and L1236 were positive for both gp80 and gp130, suggesting a possible
autocrine stimulation of STAT3. However, a further increase in STAT3
activation on IL-6 or IL-6/soluble IL-6R stimulation was
not observed. Neutralizing monoclonal antibodies against IL-6, gp80,
gp130, or both receptor subunits did not affect the proliferation or
the constitutive activation of STAT molecules in HD cell lines. However, the tyrosine kinase inhibitor AG490 blocked the constitutive activation of STAT3 and inhibited spontaneous growth of HD tumor cells.
The evidence suggests abnormal STAT signaling and growth regulation in
Hodgkin cell lines.
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