title: New Mechanism of Bone Cancer Pain: Tumor Tissue-Derived Endogenous Formaldehyde Induced Bone Cancer Pain via TRPV1 Activation.
abstract: In recent years, our serial investigations focused on the role of cancer cells-derived endogenous formaldehyde in bone cancer pain. We found that cancer cells produced formaldehyde through demethylation process by serine hydroxymethyltransferase (SHMT1 and SHMT2) and lysine-specific histone demethylase 1 (LSD1). When the cancer cells metastasized into bone marrow, the elevated endogenous formaldehyde induced bone cancer pain through activation on the transient receptor potential vanilloid subfamily member 1 (TRPV1) in the peripheral nerve fibers. More interestingly, TRPV1 expressions in the peripheral fibers were upregulated by the local insulin-like growth factor I (IGF-I) produced by the activated osteoblasts. In conclusion, tumor tissue-derived endogenous formaldehyde induced bone cancer pain via TRPV1 activation.
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, 100191, People's Republic of China. ywan@hsc.pku.edu.cn.
authors.forename: You
authors.initials: Y
authors.lastname: Wan
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000072716:Cancer Pain / Q000188:drug therapy / Q000503:physiopathology*; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D005557:Formaldehyde / Q000378:metabolism*; D012696:Glycine Hydroxymethyltransferase / Q000378:metabolism; D056466:Histone Demethylases / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000503:physiopathology / Q000556:secondary; D009363:Neoplasm Proteins / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism* / Q000503:physiopathology; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C415032:picropodophyllin; D005557:Formaldehyde; D007334:Insulin-Like Growth Factor I; D056466:Histone Demethylases; C557089:KDM1A protein, rat; D012696:Glycine Hydroxymethyltransferase; D011034:Podophyllotoxin; D002211:Capsaicin
keywords: Bone cancer pain; Formaldehyde; Insulin-like growth factor I (IGF-I); Transient receptor potential vanilloid subfamily member 1 (TRPV1)