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The distribution of cells expressing SARS-CoV-2 entry factor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human oral tissues were tested.
Yoshihiko Sawa, Soichiro Ibaragi, Tatsuo Okui, Junro Yamashita, Tetsuro Ikebe, Hiroyuki Harada Our results show that HMGB1 secreted by BC cells induces BCABP via binding to RAGE of sensory neurons and suggest that the HMGB1/RAGE axis may be a potential novel therapeutic target for BCABP.Įxpression of SARS-CoV-2 entry factors in human oral tissue. Consistent with these in vivo results, co-cultures of F11 sensory neuron-like cells with 4T1 BC cells in microfluidic culture platforms increased neurite outgrowth of F11 cells, which was blocked by HMGB1 antibody. Further, administration of a neutralizing antibody to HMGB1 or an antagonist for RAGE, FPS-ZM1, ameliorated pERK, pCREB and BCABP, while a TLR4 antagonist, TAK242, showed no effects. Importantly, silencing HMGB1 in 4T1 BC cells by shRNA reduced pERK and pCREB and BCABP with decreased HMGB1 levels in bone. Here we show that 4T1 mouse BC cells colonizing bone up-regulate the expression of molecular pain markers, phosphorylated ERK1/2 (pERK) and pCREB, in the dorsal root ganglia (DRGs) innervating bone and induced BCABP as evaluated by hind-paw mechanical hypersensitivity. A prototypic DAMP, high mobility group box 1 (HMGB1), which acts as a ligand for the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs), is increased in its expression in BC patients with poor outcomes.
Aggressive cancers secrete damage-associated molecular patterns (DAMPs) that bind to specific DAMP receptors and modulate cancer microenvironment. Although the mechanism of BC-associated bone pain (BCABP) remains poorly understood, involvement of BC products in the pathophysiology of BCABP has been proposed.
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