Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice.
Interleukin (IL) 17 is a proinflammatory cytokine secreted mainly by activated human memory CD4 T cells that induces IL-6, IL-8, and nitric oxide. Because IL-6 and IL-8 have been implicated in the pathogenesis of cervical cancer, we investigated the action of IL-17 on human cervical tumor cell lines in vitro and in vivo. We showed that in vitro, IL-17 increases IL-6 and IL-8 secretion by cervical carcinoma cell lines at both protein and mRNA levels. No direct effect of IL-17 on in vitro proliferation of cervical tumor cell lines could be demonstrated. However, two cervical cell lines transfected with a cDNA encoding IL-17 exhibited a significant increase in tumor size as compared to the parent tumor when transplanted in nude mice. This enhanced tumor growth elicited by IL-17 was associated with increased expression of IL-6 and macrophage recruitment at the tumor site. A potential role of IL-17 in modulation of the human cervical tumor phenotype was also supported by its expression on the cervical tumor in patients with CD4 infiltration. IL-17 therefore behaves like a T-cell-specific cytokine with paradoxical tumor-promoting activity. This may partially explain previous reports concerning the deleterious effect of CD4 T cells in cancer.
Tartour
E
E
Unité d'Immunologie Clinique, INSERM U 225 and Université Pierre et Marie Curie, Paris, France. etartour@curie.fr
Fossiez
F
F
Joyeux
I
I
Galinha
A
A
Gey
A
A
Claret
E
E
Sastre-Garau
X
X
Couturier
J
J
Mosseri
V
V
Vives
V
V
Banchereau
J
J
Fridman
W H
WH
Wijdenes
J
J
Lebecque
S
S
Sautès-Fridman
C
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000633:toxicity*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D002273:Carcinogens; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins