IL2 triggers a tumor progression process in a melanoma cell line MELP derived from a patient whose metastasis increased in size during IL2/INFalpha biotherapy.
Human melanomas may express both in vivo and in vitro functional IL-Rs and may be expected to directly respond to injected IL2. This may generate biological situations which may be favourable for the patient, but also for tumor progression. Here, we analyse the latter hypothesis. MELP is a melanoma cell line derived from a patient whose metastasis increased in size during IL2/IFN alpha biotherapy [correction of biotheraphy]. These cells have been characterized in vitro for their phenotype and for their sensitivity to IL2. In vitro MELP cells express an IL2-R alpha(+) beta(+) gamma(-) phenotype and IL2 treatment induces the acquisition of new functional characteristics represented (i) by the increased surface expression of two markers of metastatic evolution (ICAM-1 and CD44); (ii) by the stable induction of the IL2-R gamma with the appearance of functional IL2-R beta complex, which are also recognized by GM-CSF; (iii) by the inhibition of transcription of a regulatory cytokine such as IL6; (iv) by a differential effect of IL6 on CD44 surface expression in MELP cells treated or not with IL2 (MILG cells); (v) by the acquisition of faster growth rates and appearance of piling up and multilayer cellular organization; (vi) by the development of rapidly growing tumors in nude mice. IL2 induces in MELP cells a tumor progression process that could mimic the metastatic evolution observed in vivo during biotherapy. Therefore, MELP phenotype may help to define a subset of patients in which IL2 therapy may trigger unfavourable evolution.
Han
D
D
U 268 Inserm Hopital Paul Brousse, Villejuif Cedex, France.
Pottin-Clemenceau
C
C
Imro
M A
MA
Scudeletti
M
M
Doucet
C
C
Puppo
F
F
Brouty-Boye
D
D
Vedrenne
J
J
Sahraoui
Y
Y
Brailly
H
H
Poggi
A
A
Jasmin
C
C
Azzarone
B
B
Indiveri
F
F
D000328:Adult; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology* / Q000556:secondary / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000737:chemistry; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D016207:Cytokines; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1