In this study, a possible link between the innate immune recognition receptor TLR3 and metabolic reprogramming in Head and Neck carcinoma (HNC) cells was investigated. The effects of TLR3 stimulation/knock-down were assessed under several culture conditions in 4 HNC cell-lines by cell growth assays, targeted metabolomics, and glycolysis assays based on time-resolved analysis of proton release (Seahorse analyzer). The stimulation of TLR3 by its synthetic agonist Poly(A:U) resulted in a faster growth of HNC cells under low foetal calf serum conditions. Targeted analysis of glucose metabolism pathways demonstrated a tendency towards a shift from tricarboxylic acid cycle (Krebs cycle) to glycolysis and anabolic reactions in cells treated with Poly(A:U). Glycolysis assays confirmed that TLR3 stimulation enhanced the capacity of malignant cells to switch from oxidative phosphorylation to extra-mitochondrial glycolysis. We found evidence that HIF-1α is involved in this process: addition of the TLR3 agonist resulted in a higher cell concentration of the HIF-1α protein, even in normoxia, whereas knocking-down TLR3 resulted in a lower concentration, even in hypoxia. Finally, we assessed TLR3 expression by immunohistochemistry in a series of 7 HNSCC specimens and found that TLR3 was detected at higher levels in tumors displaying a hypoxic staining pattern. Overall, our results demonstrate that TLR3 stimulation induces the Warburg effect in HNC cells in vitro, and suggest that TLR3 may play a role in tumor adaptation to hypoxia.
1. Reliable flap even for irradiated patients 2. CT angiography with 3D reconstruction as pre-operative imaging 3. Doppler ultrasound probe to draw the artery's trajectory on skin 4. TPFF elevation concomitantly to the endoscopic procedure 5. Hemicoronal incision sufficient to harvest the TPFF 6. Superficial dissection in a plane just beneath the hair follicles 7. Dissection plane deep to the fad pad to preserve the frontal branch of the facial nerve 8. Surgical corridor wide enough to avoid any compression of the pedicle 9. Double visualization to avoid any twist and Doppler control of the STA patency 10. Close follow-up, toilet in clinics.
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