title: CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis.
abstract: Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients.
authors: Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Hongkai
authors: H
authors: Wang
authors: Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Yunyun
authors: Y
authors: Zhuo
authors: Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Xu
authors: X
authors: Hu
authors: Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Weiwei
authors: W
authors: Shen
authors: Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Ying
authors: Y
authors: Zhang
authors: Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: chtw@sina.com.
authors: Tongwei
authors: T
authors: Chu
mesh_terms: D000818:Animals; D051926:Basigin / Q000276:immunology*; D001862:Bone Resorption / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology*; D008175:Lung Neoplasms / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000276:immunology*
chemical_list: D016209:Interleukin-8; D051926:Basigin
keywords: CD147; Extracellular matrix metalloproteinase inducer; Interleukin-8; Lung cancer; Metastasis; Osteoclastogenesis