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Altered immunolocalization of FGF23 in murine femora metastasized with human breast carcinoma MDA-MB-231 cells

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Title: Altered immunolocalization of FGF23 in murine femora metastasized with human breast carcinoma MDA-MB-231 cells
Authors: Yokoyama, Ayako Browse this author
Hasegawa, Tomoka Browse this author →KAKEN DB
Hiraga, Toru Browse this author →KAKEN DB
Yamada, Tamaki Browse this author →KAKEN DB
Yimin Browse this author →KAKEN DB
Hongo, Hiromi Browse this author →KAKEN DB
Yamamoto, Tomomaya Browse this author
Abe, Miki Browse this author
Yoshida, Taiji Browse this author
Imanishi, Yasuo Browse this author →KAKEN DB
Kuroshima, Shinichiro Browse this author →KAKEN DB
Sasaki, Muneteru Browse this author →KAKEN DB
de Fraitas, Paulo Henrique Luiz Browse this author
Li, Minqi Browse this author
Amizuka, Norio Browse this author →KAKEN DB
Yamazaki, Yutaka Browse this author →KAKEN DB
Keywords: Fibroblast growth factor 23
Bone metastasis
Issue Date: 8-Apr-2021
Publisher: Springer
Journal Title: Journal of Bone and Mineral Metabolism
Volume: 39
Issue: 5
Start Page: 810
End Page: 823
Publisher DOI: 10.1007/s00774-021-01220-7
PMID: 33834310
Abstract: Introduction 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.
Rights: This 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:
Type: article (author version)
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 長谷川 智香

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