title: Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cells.
abstract: The bone is the third most common site of cancer metastasis. To invade the bone, tumor cells produce osteoclast-activating factors that increase bone resorption by osteoclasts. Here we report that human neuroblastoma cells that form osteolytic lesions in vivo do not produce osteoclast-activating factors but rather stimulate osteoclast activity in the presence of human bone marrow mesenchymal stem cells. This alternative pathway of osteoclast activation involves a nonadhesive interaction between neuroblastoma cells and bone marrow mesenchymal stem cells. Stimulated bone marrow mesenchymal stem cells express markedly increased levels of interleukin-6, which is then responsible for osteoclast activation. This report describes a critical role of bone marrow mesenchymal stem cells in bone destruction in cancer.
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Keck School of Medicine, USA.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Sohara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Cedric
authors.initials: C
authors.lastname: Minkin
authors.forename: Anat
authors.initials: A
authors.lastname: Erdreich-Epstein
authors.forename: Jan A
authors.initials: JA
authors.lastname: Nolta
authors.forename: Yves A
authors.initials: YA
authors.lastname: DeClerck
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D002450:Cell Communication; D045744:Cell Line, Tumor; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*
chemical_list: D008222:Lymphokines; C008718:osteoclast activating factor