title: TNF inhibitor suppresses bone metastasis in a breast cancer cell line.
abstract: In the evolution of cancer, tumor necrosis factor-alpha (TNF-α) plays a paradoxical role. High doses induce significant anticancer effects, but conversely, physiologic and pathologic levels of TNF-α may be involved in cancer promotion, tumor growth, and metastasis. Infliximab is a chimeric murine monoclonal antibody that binds with high affinity to soluble and membrane TNF-α and inhibits binding of TNF-α to its receptors. In the present study, we investigated the effect of infliximab, a TNF-α antagonist, on breast cancer aggressiveness and bone metastases. Infliximab greatly reduced cell motility and bone metastases in a metastatic breast cancer cell line, MDA-MB-231. The mechanism of bone metastasis inhibition involved decreased expression of CXC chemokine receptor 4 (CXCR4) and increased expression of decorin, which is the prototype of an expanding family of small leucine-rich proteoglycans. These results suggest a novel role for TNF-α inhibition in the reduction or prevention of bone metastases in this breast cancer model. Our study suggests that inhibition of TNF-α using infliximab may become a preventive therapeutic option for breast cancer.
authors.affiliation: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Wakabayashi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Matsumine
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sudo
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Uchida
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000517:prevention & control* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D000069285:Infliximab; D051379:Mice; D008807:Mice, Inbred BALB C; D011859:Radiography; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab