Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cells.
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.
Sohara
Yasuyoshi
Y
Division of Hematology-Oncology, Department of Pediatrics, Keck School of Medicine, USA.
Shimada
Hiroyuki
H
Minkin
Cedric
C
Erdreich-Epstein
Anat
A
Nolta
Jan A
JA
DeClerck
Yves A
YA
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*
D008222:Lymphokines; C008718:osteoclast activating factor