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Receptor binding and mitogenic effects of insulin and insulinlike growth factors I and II for human myeloid leukemic cells
Author(s) -
Pepe Michael G.,
Ginzton Nancy H.,
Lee Philip D. K.,
Hintz Raymond L.,
Greenberg Peter L.
Publication year - 1987
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041330204
Subject(s) - insulin , receptor , insulin receptor , myeloid , myeloid cells , microbiology and biotechnology , endocrinology , medicine , biology , chemistry , cancer research , biochemistry , insulin resistance
Abstract Insulin and insulinlike growth factors I and II (IGF‐I and IGF‐II) influence mesodermal cell proliferation and differentiation. As multiple growth factors are involved in hemopoietic cell proliferation and differentiation, we assessed the receptor binding and mitogenic effects of these peptides on a panel of mesodermally derived human myeloid leukemic cell lines. The promyelocytic cell line HL60 had the highest level of specific binding for these 125 I‐labeled ligands, with lower binding to the less differentiated myeloblast cell line KG1 and undifferentiated blast variants of these cell lines (HL60blast, KG1a). Insulin binding affinity and receptor numbers were reduced significantly by chemically induced granulocytic differentiation of HL60 cells and was unchanged following induced monocytic differentiation. No substantial alteration in IGF‐I or ‐II binding occurred with induced HL60 cell differentiation. Insulin and IGF‐I demonstrated cross competition for receptor binding and down‐regulated their homologous receptors without detectable cross modulation of the heterologous receptors on HL60 cells. IGF‐I and insulin increased HL60 cell proliferation, as assessed by 3 H‐thymidine uptake, IGF‐I> insulin. IGF‐I binding and mitogenic effects were blocked by the monoclonal anti‐IGF‐I receptor antibody IR3, indicating that IGF‐I‐induced proliferative effects were mediated via its homologous receptor. In contrast, insulin binding and mitogenesis displayed blocking by both anti‐IGI‐I and anti‐insulin receptor antibodies, indicating mediation of its activity through both receptors. These data demonstrate specific binding and mitogenic interactions between insulin, IGFs, and hemopoietic cells which are associated with their state of differentiation.