Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells

Seiko Nakayama, Ken Ichi Iida, Toyonori Tsuzuki, Toshihide Iwasiiita, Hideki Murakami, Naoya Asai, Yosuke Iwata, Masatoshi Ichihara, Shinji Ito, Kumi Kawai, Masami Asai, Ivei Kurokawa, Masahide Takahashi

Research output: Contribution to journalArticle

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Abstract

Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) mediate their actions through a unique multicomponent receptor system composed of Ret receptor tyrosine kinase and glycosyl-phosphatidylinositol- linked cell surface proteins (designated GFRα-1 and GFRα-2). In the present study, expression of these signalling components in the process of differentiation of haemopoietic cells was investigated. Ret was expressed at variable levels in normal and malignant cells of the myelomonocyte lineage. Immunohistochemical analysis of human and mouse tissues revealed that Ret expression was increased in intermediate mature myeloid cells such as promyelocytes and myelocytes and decreased in mature granulocytes and monocytes. Consistent with this observation, when THP-1 monocytic and HL-60 promyelocytic leukaemia cells expressing Ret were differentiated toward macrophages or granulocytes by treatment of 12-O-tetradecanoylphorbol-13- acetate (TPA) or all-trans retinoic acid (RA), Ret expression strikingly decreased during differentiation. Expression of GDNF, NTN, GFRα-1 and GFRα- 2 was undetectable in HP-1 and HL-60 cells as well as in bone marrow haemopoietic cells. In contrast, bone marrow stromal cells appeared to express GDNF, GFRα-1 and GFRα-2 but not Ret. These findings suggested that the interaction between stromal cells and Ret-expressing haemopoietic cells in the bone marrow microenvironment may play a role in the differentiation of myelomonocyte-lineage cells through activation of the GDNF/Ret signalling pathway.

Original languageEnglish
Pages (from-to)50-57
Number of pages8
JournalBritish Journal of Haematology
Volume105
Issue number1
DOIs
Publication statusPublished - 06-05-1999

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Glial Cell Line-Derived Neurotrophic Factor
Bone Marrow Cells
Neurturin
Granulocyte Precursor Cells
Granulocytes
Glycosylphosphatidylinositols
HL-60 Cells
Receptor Protein-Tyrosine Kinases
Tetradecanoylphorbol Acetate
Cell Lineage
Myeloid Cells
Stromal Cells
Tretinoin
Mesenchymal Stromal Cells
Monocytes
Cell Differentiation
Membrane Proteins
Leukemia
Macrophages

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Nakayama, Seiko ; Iida, Ken Ichi ; Tsuzuki, Toyonori ; Iwasiiita, Toshihide ; Murakami, Hideki ; Asai, Naoya ; Iwata, Yosuke ; Ichihara, Masatoshi ; Ito, Shinji ; Kawai, Kumi ; Asai, Masami ; Kurokawa, Ivei ; Takahashi, Masahide. / Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells. In: British Journal of Haematology. 1999 ; Vol. 105, No. 1. pp. 50-57.
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title = "Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells",
abstract = "Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) mediate their actions through a unique multicomponent receptor system composed of Ret receptor tyrosine kinase and glycosyl-phosphatidylinositol- linked cell surface proteins (designated GFRα-1 and GFRα-2). In the present study, expression of these signalling components in the process of differentiation of haemopoietic cells was investigated. Ret was expressed at variable levels in normal and malignant cells of the myelomonocyte lineage. Immunohistochemical analysis of human and mouse tissues revealed that Ret expression was increased in intermediate mature myeloid cells such as promyelocytes and myelocytes and decreased in mature granulocytes and monocytes. Consistent with this observation, when THP-1 monocytic and HL-60 promyelocytic leukaemia cells expressing Ret were differentiated toward macrophages or granulocytes by treatment of 12-O-tetradecanoylphorbol-13- acetate (TPA) or all-trans retinoic acid (RA), Ret expression strikingly decreased during differentiation. Expression of GDNF, NTN, GFRα-1 and GFRα- 2 was undetectable in HP-1 and HL-60 cells as well as in bone marrow haemopoietic cells. In contrast, bone marrow stromal cells appeared to express GDNF, GFRα-1 and GFRα-2 but not Ret. These findings suggested that the interaction between stromal cells and Ret-expressing haemopoietic cells in the bone marrow microenvironment may play a role in the differentiation of myelomonocyte-lineage cells through activation of the GDNF/Ret signalling pathway.",
author = "Seiko Nakayama and Iida, {Ken Ichi} and Toyonori Tsuzuki and Toshihide Iwasiiita and Hideki Murakami and Naoya Asai and Yosuke Iwata and Masatoshi Ichihara and Shinji Ito and Kumi Kawai and Masami Asai and Ivei Kurokawa and Masahide Takahashi",
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Nakayama, S, Iida, KI, Tsuzuki, T, Iwasiiita, T, Murakami, H, Asai, N, Iwata, Y, Ichihara, M, Ito, S, Kawai, K, Asai, M, Kurokawa, I & Takahashi, M 1999, 'Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells', British Journal of Haematology, vol. 105, no. 1, pp. 50-57. https://doi.org/10.1111/j.1365-2141.1999.01311.x

Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells. / Nakayama, Seiko; Iida, Ken Ichi; Tsuzuki, Toyonori; Iwasiiita, Toshihide; Murakami, Hideki; Asai, Naoya; Iwata, Yosuke; Ichihara, Masatoshi; Ito, Shinji; Kawai, Kumi; Asai, Masami; Kurokawa, Ivei; Takahashi, Masahide.

In: British Journal of Haematology, Vol. 105, No. 1, 06.05.1999, p. 50-57.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells

AU - Nakayama, Seiko

AU - Iida, Ken Ichi

AU - Tsuzuki, Toyonori

AU - Iwasiiita, Toshihide

AU - Murakami, Hideki

AU - Asai, Naoya

AU - Iwata, Yosuke

AU - Ichihara, Masatoshi

AU - Ito, Shinji

AU - Kawai, Kumi

AU - Asai, Masami

AU - Kurokawa, Ivei

AU - Takahashi, Masahide

PY - 1999/5/6

Y1 - 1999/5/6

N2 - Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) mediate their actions through a unique multicomponent receptor system composed of Ret receptor tyrosine kinase and glycosyl-phosphatidylinositol- linked cell surface proteins (designated GFRα-1 and GFRα-2). In the present study, expression of these signalling components in the process of differentiation of haemopoietic cells was investigated. Ret was expressed at variable levels in normal and malignant cells of the myelomonocyte lineage. Immunohistochemical analysis of human and mouse tissues revealed that Ret expression was increased in intermediate mature myeloid cells such as promyelocytes and myelocytes and decreased in mature granulocytes and monocytes. Consistent with this observation, when THP-1 monocytic and HL-60 promyelocytic leukaemia cells expressing Ret were differentiated toward macrophages or granulocytes by treatment of 12-O-tetradecanoylphorbol-13- acetate (TPA) or all-trans retinoic acid (RA), Ret expression strikingly decreased during differentiation. Expression of GDNF, NTN, GFRα-1 and GFRα- 2 was undetectable in HP-1 and HL-60 cells as well as in bone marrow haemopoietic cells. In contrast, bone marrow stromal cells appeared to express GDNF, GFRα-1 and GFRα-2 but not Ret. These findings suggested that the interaction between stromal cells and Ret-expressing haemopoietic cells in the bone marrow microenvironment may play a role in the differentiation of myelomonocyte-lineage cells through activation of the GDNF/Ret signalling pathway.

AB - Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) mediate their actions through a unique multicomponent receptor system composed of Ret receptor tyrosine kinase and glycosyl-phosphatidylinositol- linked cell surface proteins (designated GFRα-1 and GFRα-2). In the present study, expression of these signalling components in the process of differentiation of haemopoietic cells was investigated. Ret was expressed at variable levels in normal and malignant cells of the myelomonocyte lineage. Immunohistochemical analysis of human and mouse tissues revealed that Ret expression was increased in intermediate mature myeloid cells such as promyelocytes and myelocytes and decreased in mature granulocytes and monocytes. Consistent with this observation, when THP-1 monocytic and HL-60 promyelocytic leukaemia cells expressing Ret were differentiated toward macrophages or granulocytes by treatment of 12-O-tetradecanoylphorbol-13- acetate (TPA) or all-trans retinoic acid (RA), Ret expression strikingly decreased during differentiation. Expression of GDNF, NTN, GFRα-1 and GFRα- 2 was undetectable in HP-1 and HL-60 cells as well as in bone marrow haemopoietic cells. In contrast, bone marrow stromal cells appeared to express GDNF, GFRα-1 and GFRα-2 but not Ret. These findings suggested that the interaction between stromal cells and Ret-expressing haemopoietic cells in the bone marrow microenvironment may play a role in the differentiation of myelomonocyte-lineage cells through activation of the GDNF/Ret signalling pathway.

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