Cutaneous T-cell lymphoma cells are sensitive to rapamycin.
Cutaneous T-cell lymphomas (CTCL) are characterised by clonal expansion of helper T lymphocytes that infiltrate the skin. Only a small number of cell lines exist to study cellular pathways leading to T-cell transformation and to identify new targets for intervention. We wanted to investigate the inhibition of mTOR as a possible therapeutic target in CTCL. Primary cells of patients with Sézary syndrome (SS) and conventional CTCL cell lines were analysed. Constitutive activation of mTOR was found, and concomitantly, we could show that rapamycin, a specific inhibitor of mTOR, inhibits CTCL cell growth in vitro by induction of cell cycle arrest. Using a previously established animal model for CTCL, we additionally observed upon rapamycin treatment tumor growth inhibition in vivo. In summary, primary cells from patients with SS as well as CTCL cell lines allowed us to identify mTOR as an important target for intervention.
Kremer
Melanie
M
Paul-Ehrlich-Institut, Paul-Ehrlich, Langen, Germany.
Sliva
Katja
K
Klemke
Claus-Detlev
CD
Schnierle
Barbara S
BS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012751:Sezary Syndrome / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus