Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast-like cell formation in vitro.
Cancer cells metastasized to bone induce osteoclastogenesis for bone destruction. Coculture of either mouse melanoma B16 or breast cancer Balb/c-MC cells with mouse bone marrow cells (BMCs) induced osteoclast-like cells, which were not observed when cancer cells were segregated from BMCs. Osteoclast differentiation factor (ODF), also known as receptor activator of NF-kappaB ligand (RANKL), is a direct mediator of many osteotropic factors. Neither BMCs, B16 nor Balb/c-MC cells alone expressed ODF mRNA. However, coculture of these cancer cells with BMCs induced ODF expression, which was prevented by indomethacin. Moreover, the coculture with cancer cells inhibited secretion of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF), an inhibitory decoy receptor for ODF, from BMCs. Thus, enhanced osteoclastogenesis in the presence of cancer cells might be due to an increase in ODF activity. These results suggest that interactions between cancer cells and BMCs induce ODF expression and suppress OPG/OCIF level in metastatic foci resulting in pathological osteoclastogenesis for bone destruction.
Chikatsu
N
N
Division of Endocrinology, University of Tokyo School of Medicine, Tokyo, 112-8688, Japan.
Takeuchi
Y
Y
Tamura
Y
Y
Fukumoto
S
S
Yano
K
K
Tsuda
E
E
Ogata
E
E
Fujita
T
T
D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000473:pathology*; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D002352:Carrier Proteins / Q000235:genetics*; D002448:Cell Adhesion; D018920:Coculture Techniques; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor
D002352:Carrier Proteins; D017931:DNA Primers; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D007213:Indomethacin