Breast cancer cell line MDA-231 stimulates osteoclastogenesis and bone resorption in human osteoclasts.
Breast cancers commonly cause osteolytic metastases in bone, a process that is dependent upon osteoclast-mediated bone resorption, but the mechanism responsible for tumor-mediated osteoclast activation has not yet been clarified. In the present study we utilized a well-known human breast cancer cell line (MDA-231) in order to assess its capability to influence osteoclastogenesis in human bone marrow cultures and bone resorption in fully differentiated osteoclasts. We demonstrated that conditioned medium (CM) harvested from MDA-231 increased the formation of multinucleated TRAP-positive cells in bone marrow cultures. Bone resorption activity of fully differentiated human osteoclasts and of osteoclast-like cell lines, from giant cell tumors of bone (GCT), was highly increased by the presence of MDA-231 CM. Moreover, while MDA-231 by themselves did not produce IL-6 tumor cell, CM increased the secretion of IL-6 by primary human osteoclasts and GCT cell lines compared to untreated controls. These data suggest that MDA-231 produce osteoclastic activating factor(s) that increase both osteoclast formation in bone marrow culture and bone resorption activity by mature cells. Moreover, breast cancer cells stimulate IL-6 secretion by osteoclasts that is one of the factors known to supports osteoclastogenesis.
Grano
M
M
Department of Human Anatomy and Histology, University of Bari, Bari, 11-70124, Italy.
Mori
G
G
Minielli
V
V
Cantatore
F P
FP
Colucci
S
S
Zallone
A Z
AZ
D000135:Acid Phosphatase / Q000378:metabolism; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology*; D001859:Bone Neoplasms; D001862:Bone Resorption; D001943:Breast Neoplasms; D006528:Carcinoma, Hepatocellular; D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D005870:Giant Cell Tumors; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008113:Liver Neoplasms; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis; D000071681:Tartrate-Resistant Acid Phosphatase; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D017077:Culture Media, Conditioned; D007527:Isoenzymes; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase