Activation of Toll-like receptors 2, 3, and 4 on human melanoma cells induces inflammatory factors.
Toll-like receptors (TLR) have been shown to be expressed on various types of cancers; however, their functional activity is not known. We examined TLR profiles of human melanoma cells and showed that TLR2, TLR3, and TLR4 were found to be highly expressed. By PCR array analysis, specific stimulation of TLR2, TLR3, and TLR4 on melanoma cells showed significant activation of the adaptor protein MyD88, as well as downstream signal transduction factors nuclear factor-kappaB and inflammatory response-related factors. Specific ligand activation of TLR2, TLR3, and TLR4 was shown to induce cell migration. Peripheral blood lymphocytes and melanoma purified RNA was shown to activate TLR3 on melanoma cells. These studies show expression and functional activity of specific TLRs on melanoma cells and as potential therapeutic targets to control tumor progression.
Goto
Yasufumi
Y
Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA.
Arigami
Takaaki
T
Kitago
Minoru
M
Nguyen
Sandy L
SL
Narita
Norihiko
N
Ferrone
Soldano
S
Morton
Donald L
DL
Irie
Reiko F
RF
Hoon
Dave S B
DS
D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D018836:Inflammation Mediators; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4