The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis

Tatsuki Uchiyama, Hiroshi Kawabata, Yasuo Miura, Satoshi Yoshioka, Masaki Iwasa, Hisayuki Yao, Soichiro Sakamoto, Masakazu Fujimoto, Hironori Haga, Norimitsu Kadowaki, Taira Maekawa, Akifumi Takaori-Kondo

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

抄録

Growth differentiation factor 15 (GDF15) is a pleiotropic cytokine that belongs to the transforming growth factor-β superfamily. Elevated serum concentrations of this cytokine have been reported in patients with various malignancies. To assess the potential roles of GDF15 in hematologic malignancies, we measured its serum levels in patients with these diseases. We found that serum GDF15 levels were elevated in almost all these patients, particularly in patients with primary myelofibrosis (PMF). Immunohistochemical staining of bone marrow (BM) specimens revealed that GDF15 was strongly expressed by megakaryocytes, which may be sources of increased serum GDF15 in PMF patients. Therefore, we further assessed the contribution of GDF15 to the pathogenesis of PMF. Recombinant human (rh) GDF15 enhanced the growth of human BM mesenchymal stromal cells (BM-MSCs), and it enhanced the potential of these cells to support human hematopoietic progenitor cell growth in a co-culture system. rhGDF15 enhanced the growth of human primary fibroblasts, but it did not affect their expression of profibrotic genes. rhGDF15 induced osteoblastic differentiation of BM-MSCs in vitro, and pretreatment of BM-MSCs with rGDF15 enhanced the induction of bone formation in a xenograft mouse model. These results suggest that serum levels of GDF15 in PMF are elevated, that megakaryocytes are sources of this cytokine in BM, and that GDF15 may modulate the pathogenesis of PMF by enhancing proliferation and promoting osteogenic differentiation of BM-MSCs.

元の言語英語
ページ(範囲)1558-1572
ページ数15
ジャーナルCancer Medicine
4
発行部数10
DOI
出版物ステータス出版済み - 10 2015

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Growth Differentiation Factor 15
Primary Myelofibrosis
Bone Marrow
Serum
Megakaryocytes
Cytokines
Mesenchymal Stromal Cells
Growth
Bone Development
Transforming Growth Factors
Hematologic Neoplasms
Hematopoietic Stem Cells
Coculture Techniques
Heterografts
Osteogenesis
Fibroblasts

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

これを引用

Uchiyama, T., Kawabata, H., Miura, Y., Yoshioka, S., Iwasa, M., Yao, H., ... Takaori-Kondo, A. (2015). The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis. Cancer Medicine, 4(10), 1558-1572. https://doi.org/10.1002/cam4.502

The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis. / Uchiyama, Tatsuki; Kawabata, Hiroshi; Miura, Yasuo; Yoshioka, Satoshi; Iwasa, Masaki; Yao, Hisayuki; Sakamoto, Soichiro; Fujimoto, Masakazu; Haga, Hironori; Kadowaki, Norimitsu; Maekawa, Taira; Takaori-Kondo, Akifumi.

:: Cancer Medicine, 巻 4, 番号 10, 10.2015, p. 1558-1572.

研究成果: ジャーナルへの寄稿記事

Uchiyama, T, Kawabata, H, Miura, Y, Yoshioka, S, Iwasa, M, Yao, H, Sakamoto, S, Fujimoto, M, Haga, H, Kadowaki, N, Maekawa, T & Takaori-Kondo, A 2015, 'The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis', Cancer Medicine, 巻. 4, 番号 10, pp. 1558-1572. https://doi.org/10.1002/cam4.502
Uchiyama, Tatsuki ; Kawabata, Hiroshi ; Miura, Yasuo ; Yoshioka, Satoshi ; Iwasa, Masaki ; Yao, Hisayuki ; Sakamoto, Soichiro ; Fujimoto, Masakazu ; Haga, Hironori ; Kadowaki, Norimitsu ; Maekawa, Taira ; Takaori-Kondo, Akifumi. / The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis. :: Cancer Medicine. 2015 ; 巻 4, 番号 10. pp. 1558-1572.
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abstract = "Growth differentiation factor 15 (GDF15) is a pleiotropic cytokine that belongs to the transforming growth factor-β superfamily. Elevated serum concentrations of this cytokine have been reported in patients with various malignancies. To assess the potential roles of GDF15 in hematologic malignancies, we measured its serum levels in patients with these diseases. We found that serum GDF15 levels were elevated in almost all these patients, particularly in patients with primary myelofibrosis (PMF). Immunohistochemical staining of bone marrow (BM) specimens revealed that GDF15 was strongly expressed by megakaryocytes, which may be sources of increased serum GDF15 in PMF patients. Therefore, we further assessed the contribution of GDF15 to the pathogenesis of PMF. Recombinant human (rh) GDF15 enhanced the growth of human BM mesenchymal stromal cells (BM-MSCs), and it enhanced the potential of these cells to support human hematopoietic progenitor cell growth in a co-culture system. rhGDF15 enhanced the growth of human primary fibroblasts, but it did not affect their expression of profibrotic genes. rhGDF15 induced osteoblastic differentiation of BM-MSCs in vitro, and pretreatment of BM-MSCs with rGDF15 enhanced the induction of bone formation in a xenograft mouse model. These results suggest that serum levels of GDF15 in PMF are elevated, that megakaryocytes are sources of this cytokine in BM, and that GDF15 may modulate the pathogenesis of PMF by enhancing proliferation and promoting osteogenic differentiation of BM-MSCs.",
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AU - Iwasa, Masaki

AU - Yao, Hisayuki

AU - Sakamoto, Soichiro

AU - Fujimoto, Masakazu

AU - Haga, Hironori

AU - Kadowaki, Norimitsu

AU - Maekawa, Taira

AU - Takaori-Kondo, Akifumi

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