Effect of ultraviolet-inducible cytokines on melanoma growth in vivo: stimulation of melanoma growth by interleukin-1 and -6.
Ultraviolet light of wavelengths 280-320 nm (UVB) can induce transcription of cytokine mRNAs and increase expression of the corresponding proteins in the epidermis. In particular, UVB can stimulate keratinocyte synthesis of interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). Several of these cytokines can influence the growth of tumour cells as well as the host response to these tumours. In this study we examined the effect of IL-1, IL-6, IL-8, TNF-alpha and TGF-beta on the growth of melanoma in vivo and in vitro, using the murine B16 melanoma and its syngeneic host, the C57BL/6 mouse. Mice were injected with 0.1-1.5 micrograms of recombinant cytokine subcutaneously every other day following a subcutaneous injection of 1 x 10(5) B16 cells (F-10 clone). In this model, tumours appeared within 12-14 days, and IL-1 and IL-6 stimulated tumour growth in vivo. TNF-alpha, TGF-beta, IL-2 and IL-8 had no significant effect. In contrast to the in vivo effects, TNF-alpha inhibited B16 cell growth in vitro and IL-6 stimulated B16 cell growth. The in vivo IL-1 effect on tumour growth in mice was examined in greater detail. IL-1-treated animals showed tumours approximately 5-fold greater in size than those of the control animals. The IL-1-treated animals also showed highly vascularized tumours that invaded underlying muscle tissue more rapidly than controls. These tumors also showed a strong positive reaction with antibody to intercellular adhesion molecule-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Mckenzie
R C
RC
Division of Dermatology, University of Toronto, Sunnybrook Health Science Centre, Ontario, Canada.
Park
E S
ES
Brown
W R
WR
Shivji
G S
GS
Sauder
D N
DN
D000818:Animals; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology* / Q000528:radiation effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology* / Q000528:radiation effects*; D015850:Interleukin-6 / Q000494:pharmacology* / Q000528:radiation effects*; D008546:Melanoma, Experimental / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000473:pathology / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000528:radiation effects; D014466:Ultraviolet Rays
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha