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Immunolocalization of FGF23 in bone metastasis of human breast carcinoma MDA231 cells
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| Title: | Immunolocalization of FGF23 in bone metastasis of human breast carcinoma MDA231 cells |
| Other Titles: | 乳がんMDA231細胞の骨転移巣におけるFGF23の免疫局在について |
| Authors: | 横山, 亜矢子 Browse this author |
| Keywords: | bone metastasis | | FGF23 | | MDA231 cell | | osteocyte | | ENPP1 |
| Issue Date: | 25-Mar-2019 |
| Publisher: | Hokkaido University |
| Abstract: | After the onset of bone metastasis, the tumor cells appear to make surrounding microenvironments, including systemic and local serum concentrations of inorganic phosphate (Pi), suitable for their proliferation, matrix degradation, and nest expansion. In this study, we attempted to clarify if bone-metastasized tumors affect the localization of serum Pi concentration regulatory factors. Using femoral metastatic lesions of BALB/c nu/nu mice at one month after the intracardiac injection of human breast carcinoma MDA231 cells, we examined the immunolocalization of fibroblast growth factor (FGF) 23 and FGFR1/αklotho, which are involved in regulating serum concentration of Pi by cooperating with kidney, and of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), tissue nonspecific alkaline phosphatase (TNALP), and PHOSPHO1, which regulate the local synthesis of Pi. In the metastatic lesions of femoral metaphyses, many tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts accumulated on osteopontin-reactive scalloped trabecular surfaces, indicating active osteolytic metastasis. Although MDA231 cells showed very weak FGF23 immunoreactivity when cultured in vitro, MDA231 cells revealed intense FGF23 -reactivity in the metastasized lesions. Despite significantly- elevated serum FGF23 levels, there was no significant decrease in the serum concentration of Pi in nu/nu mice with bone-metastasized tumor when compared with the control mice and mice injected with MDA231 cells in mammary glands. Interestingly, FGF23 was abundantly synthesized in the bone-metastasized MDA231 cells, while osteocytes in bone adjacent to the FGF23-immunopositive tumor nests were negative for FGF23. Unlike the reduced synthesis of FGF23 in osteocytes, the osteocytes proximal to MDA231 cells were shown to synthesize dentin matrix protein (DMP)-1. Therefore, it seems possible that the abundant FGF23 secreted by MDA231 cells inhibits the surrounding osteocytes from synthesizing FGF23. In addition, immunopositivity of ENPP1 but not TNALP or PHOSPHO1 was broadly seen mainly in fibroblastic stromal cells in metastatic lesions, indicating that ENPP1 would be useful for bone-metastasized MDA231 cells. Taken together, it seems likely that rather than affecting the serum concentration of Pi, FGF23 plays some local roles in establishing suitable conditions favoring the metastasis of MDA231 cells in the bone in an autocrine/paracrine manner. |
| Conffering University: | 北海道大学 |
| Degree Report Number: | 甲第13489号 |
| Degree Level: | 博士 |
| Degree Discipline: | 歯学 |
| Examination Committee Members: | (主査) 教授 山崎 裕, 教授 網塚 憲生, 教授 樋田 京子, 助教 長谷川 智香 |
| Degree Affiliation: | 歯学研究科(口腔医学専攻) |
| Type: | theses (doctoral) |
| URI: | http://hdl.handle.net/2115/91596 |
| Appears in Collections: | 課程博士 (Doctorate by way of Advanced Course) > 歯学院(Graduate School of Dental Medicine)
学位論文 (Theses) > 博士 （歯学）
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