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Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells
Author(s) -
Nakayama Seiko,
Iida Kenichi,
Tsuzuki Toyonori,
Iwashita Toshihide,
Murakami Hideki,
Asai Naoya,
Iwata Yosuke,
Ichihara Masatoshi,
Ito Shinji,
Kawai Kumi,
Asai Masami,
Kurokawa Kei,
Takahashi Masahide
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1999.01311.x
Subject(s) - glial cell line derived neurotrophic factor , stromal cell , bone marrow , cellular differentiation , biology , microbiology and biotechnology , myeloid , cell culture , neurotrophic factors , cancer research , receptor , immunology , biochemistry , gene , genetics
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 THP‐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.