title: Variability of the paracrine-induced osteoclastogenesis by human breast cancer cell lines.
abstract: Breast cancer frequently metastasizes to the bone, often leading to the formation of osteolytic lesions. This work compares the paracrine-induced osteoclastogenesis mediated by four human breast cancer cell lines, the estrogen-receptor positive T47D and MCF-7 and the estrogen-negative SK-BR-3 and Hs-578T cell lines. Human osteoclast precursor cells were cultured in the presence of conditioned media from the breast cancer cell lines (10% and 20%), collected at different culture periods (48 h, 7 days, and 14 days). Cultures performed in the absence or the presence of M-CSF and RANKL served as negative and positive control, respectively. Results showed that the cell lines differentially expressed several osteoclastogenic genes. All cell lines exhibited a significant osteoclastogenic potential, evidenced by a high TRAP activity and number of osteoclastic cells, expression of several osteoclast-related genes, and, particularly, a high calcium phosphate resorption activity. Differences among the osteoclastogenic potential of the cell lines were noted. T47D and MCF-7 cell lines displayed the highest and the lowest osteoclastogenic response, respectively. Despite the variability observed, MEK and NF-κB signaling pathways, and, at a lesser extent, PGE2 production, seemed to have a central role on the observed osteoclastogenic response. In conclusion, the tested breast cancer cell lines exhibited a high osteoclastogenic potential, although with some variability on the cell response profile, a factor to be considered in the development of new therapeutic approaches for breast cancer-induced bone metastasis.
authors.affiliation: Laboratório de Farmacologia e Biocompatibilidade Celular, Faculdade de Medicina Dentária, Universidade do Porto, Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Costa-Rodrigues
authors.forename: Karen A
authors.initials: KA
authors.lastname: Moniz
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.forename: Maria H
authors.initials: MH
authors.lastname: Fernandes
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000199:Actins / Q000032:analysis; D001862:Bone Resorption; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D010010:Osteoclasts / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D019899:Paracrine Communication; D018003:Receptors, Calcitonin / Q000032:analysis; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D019096:Vitronectin / Q000032:analysis
chemical_list: D000199:Actins; D007527:Isoenzymes; D018003:Receptors, Calcitonin; D019096:Vitronectin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase