title: CCL5 and CCR5 interaction promotes cell motility in human osteosarcoma.
abstract: BACKGROUND
  Osteosarcoma is characterized by a high malignant and metastatic potential. CCL5 (previously called RANTES) was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells. It has been reported that the effect of CCL5 is mediated via CCR receptors. However, the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells is mostly unknown.
  
  
  RESULTS
  Here we found that CCL5 increased the migration and expression of αvβ3 integrin in human osteosarcoma cells. Stimulation of cells with CCL5 increased CCR5 but not CCR1 and CCR3 expression. CCR5 mAb, inhibitor, and siRNA reduced the CCL5-enhanced the migration and integrin up-regulation of osteosarcoma cells. Activations of MEK, ERK, and NF-κB pathways after CCL5 treatment were demonstrated, and CCL5-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK, and NF-κB cascades. In addition, over-expression of CCL5 shRNA inhibited the migratory ability and integrin expression in osteosarcoma cells.
  
  
  CONCLUSIONS
  CCL5 and CCR5 interaction acts through MEK, ERK, which in turn activates NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human osteosarcoma cells.
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Wang
authors.forename: Hsing-Hsien
authors.initials: HH
authors.lastname: Wu
authors.forename: Shih-Chia
authors.initials: SC
authors.lastname: Liu
authors.forename: Po-Chuan
authors.initials: PC
authors.lastname: Wang
authors.forename: Wen-Chieh
authors.initials: WC
authors.lastname: Ou
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Chou
authors.forename: Yung-Shuen
authors.initials: YS
authors.lastname: Shen
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018946:Chemokine CCL5 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology*; D054388:Receptors, CCR / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D039302:Integrin alphaVbeta3; D016328:NF-kappa B; D054388:Receptors, CCR; D019713:Receptors, CCR5; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases