title: Functionally active toll-like receptor 3 on human primary and metastatic cancer cells.
abstract: Toll-like receptor 3 (TLR3) is a member of Toll-like receptors who recognize structurally conserved molecules derived from pathogens and trigger the immune response. To clarify if TLR3, is expressed in certain tumour cell lines and whether it is functional and what is the response of these cell lines to different concentrations of poly I:C treatment, we have screened SW480, SW620, FaDu and Detroit 562 cell lines using real-time PCR, flow cytometry and ELISA. We have shown that all these cell lines express TLR3 on mRNA and protein level but it is only functional in Detroit 562 cell line since only in these cells poly I:C treatment triggered the IL-6 secretion. In addition, poly I:C treatment inhibited cell growth and triggered up-regulation of IL-12p40, IL-8 and Il-1alpha in Detroit 562 cell line. By using annexin-V apoptosis detection kit, we have found that poly I:C triggers apoptosis in Detroit 562 cell line. We have found here that based on the results of TLR3 functionality there is a huge difference between FaDu and Detroit 562 cell lines which are of the same origin (pharynx) but FaDu is primary and Detroit 562 metastatic carcinoma. Our study also shows that Detroit 562 cell line could be a good model for cancer therapy research and development as it is responsive to TLR3 agonists which consequently drives it to apoptosis.
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
authors.forename: T
authors.initials: T
authors.lastname: Matijevic
authors.forename: M
authors.initials: M
authors.lastname: Marjanovic
authors.forename: J
authors.initials: J
authors.lastname: Pavelic
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000473:pathology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011070:Poly I-C / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: D007369:Interferon Inducers; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C