2024-03-29T04:57:42Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/847402022-11-17T02:08:08Zhdl_2115_20042hdl_2115_136Altered immunolocalization of FGF23 in murine femora metastasized with human breast carcinoma MDA-MB-231 cellsYokoyama, AyakoHasegawa, TomokaHiraga, ToruYamada, TamakiYiminHongo, HiromiYamamoto, TomomayaAbe, MikiYoshida, TaijiImanishi, YasuoKuroshima, ShinichiroSasaki, Muneterude Fraitas, Paulo Henrique LuizLi, MinqiAmizuka, NorioYamazaki, YutakaFibroblast growth factor 23OsteocyteImmunohistochemistryBone metastasisMDA-MB-231497Introduction After the onset of bone metastasis, tumor cells appear to modify surrounding microenvironments for their benefit, and particularly, the levels of circulating fibroblast growth factor (FGF) 23 in patients with tumors have been highlighted. Materials and methods We have attempted to verify if human breast carcinoma MDA-MB-231 cells metastasized in the long bone of nu/nu mice would synthesize FGF23. Serum concentrations of calcium, phosphate (Pi) and FGF23 were measured in control nu/nu mice, bone-metastasized mice, and mice with mammary gland injected with MDA-MB-231 cells mimicking primary mammary tumors. Results and conclusions MDA-MB-231 cells revealed intense FGF23 reactivity in metastasized lesions, whereas MDA-MB-231 cells cultured in vitro or when injected into the mammary glands (without bone metastasis) showed weak FGF23 immunoreactivity. Although the bone-metastasized MDA-MB-231 cells abundantly synthesized FGF23, osteocytes adjacent to the FGF23-immunopositive tumors, unlike intact osteocytes, showed no FGF23. Despite significantly elevated serum FGF23 levels in bone-metastasized mice, there was no significant decrease in the serum Pi concentration when compared with the intact mice and mice with a mass of MDA-MB-231 cells in mammary glands. The metastasized femora showed increased expression and FGFR1 immunoreactivity in fibroblastic stromal cells, whereas femora of control mice showed no obvious FGFR1 immunoreactivity. Taken together, it seems likely that MDA-MB-231 cells synthesize FGF23 when metastasized to a bone, and thus affect FGFR1-positive stromal cells in the metastasized tumor nest in a paracrine manner.SpringerJournal Articleapplication/pdfhttp://hdl.handle.net/2115/84740https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/84740/1/Yokoyama%20et%20al%2c%20JBMM%2c%202021.pdf0914-8779AA10747551Journal of Bone and Mineral Metabolism3958108232021-04-08enginfo:pmid/33834310info:doi/10.1007/s00774-021-01220-7This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00774-021-01220-7author