author_facet Villunger, Andreas
Egle, Alexander
Kos, Marion
Egle, Daniel
Tinhofer, Inge
Henn, Traudl
Überall, Florian
Maly, Karl
Greil, Richard
Villunger, Andreas
Egle, Alexander
Kos, Marion
Egle, Daniel
Tinhofer, Inge
Henn, Traudl
Überall, Florian
Maly, Karl
Greil, Richard
author Villunger, Andreas
Egle, Alexander
Kos, Marion
Egle, Daniel
Tinhofer, Inge
Henn, Traudl
Überall, Florian
Maly, Karl
Greil, Richard
spellingShingle Villunger, Andreas
Egle, Alexander
Kos, Marion
Egle, Daniel
Tinhofer, Inge
Henn, Traudl
Überall, Florian
Maly, Karl
Greil, Richard
British Journal of Haematology
Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
Hematology
author_sort villunger, andreas
spelling Villunger, Andreas Egle, Alexander Kos, Marion Egle, Daniel Tinhofer, Inge Henn, Traudl Überall, Florian Maly, Karl Greil, Richard 0007-1048 1365-2141 Wiley Hematology http://dx.doi.org/10.1046/j.1365-2141.1998.00880.x <jats:p>It has been shown that granulocyte/macrophage colony stimulating factor (GM‐CSF) is able to support myeloma cell propagation in cooperation with interleukin (IL)‐6, the major growth factor for malignant plasma cells, although the biological mechanisms involved remain unknown. Therefore we investigated (i) the expression levels of the GM‐CSF receptor (GM‐CSFR) constituents in three malignant plasma cell lines and in native malignant plasma cells, (ii) the ability of the receptor to mediate common signalling pathways regulating proliferation and cell survival in malignant plasma cell lines, and (iii) the effects of GM‐CSF on tumour cell biology.</jats:p><jats:p>The GM‐CSFRα subunit was detected in the malignant plasma cell lines RPMI‐8226, MC/CAR, IM‐9 as well as 6/6 native myeloma cell samples derived from the bone marrow of patients with overt disease. Furthermore, GM‐CSFR expression was also detected in the CD19<jats:sup>+</jats:sup> fraction from 2/3 bone marrow samples and 5/8 peripheral blood samples derived from patients with malignant plasma cell disorders, but not in the CD19<jats:sup>+</jats:sup> fraction of peripheral blood from healthy donors. The expressed cytokine receptor α‐subunit was able to constitute a functional signalling complex with the ubiquitously expressed GM‐CSFRβ subunit, as demonstrated by the fact that GM‐CSF induced the p21‐ras/mitogen‐activated protein kinase (MAPK) signalling cascade in malignant plasma cell lines. Since this signalling cascade plays an essential role in the mediation of both proliferation and cell survival, we investigated the impact of GM‐CSF on these two events. Application of GM‐CSF led to an increase of DNA‐synthesis in MC/CAR, IM‐9 and RPMI‐8226 cells. Furthermore, it increased longevity of these malignant plasma cell lines by reducing the rates of spontaneous apoptosis. We conclude that (i) the functional GM‐CSFR is commonly expressed on malignant plasma cells and that (ii) GM‐CSF promotes the clonal expansion of myeloma cells by inhibiting spontaneous apoptosis and promoting DNA synthesis.</jats:p> Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity British Journal of Haematology
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series British Journal of Haematology
source_id 49
title Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_unstemmed Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_full Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_fullStr Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_full_unstemmed Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_short Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_sort functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
topic Hematology
url http://dx.doi.org/10.1046/j.1365-2141.1998.00880.x
publishDate 1998
physical 1069-1080
description <jats:p>It has been shown that granulocyte/macrophage colony stimulating factor (GM‐CSF) is able to support myeloma cell propagation in cooperation with interleukin (IL)‐6, the major growth factor for malignant plasma cells, although the biological mechanisms involved remain unknown. Therefore we investigated (i) the expression levels of the GM‐CSF receptor (GM‐CSFR) constituents in three malignant plasma cell lines and in native malignant plasma cells, (ii) the ability of the receptor to mediate common signalling pathways regulating proliferation and cell survival in malignant plasma cell lines, and (iii) the effects of GM‐CSF on tumour cell biology.</jats:p><jats:p>The GM‐CSFRα subunit was detected in the malignant plasma cell lines RPMI‐8226, MC/CAR, IM‐9 as well as 6/6 native myeloma cell samples derived from the bone marrow of patients with overt disease. Furthermore, GM‐CSFR expression was also detected in the CD19<jats:sup>+</jats:sup> fraction from 2/3 bone marrow samples and 5/8 peripheral blood samples derived from patients with malignant plasma cell disorders, but not in the CD19<jats:sup>+</jats:sup> fraction of peripheral blood from healthy donors. The expressed cytokine receptor α‐subunit was able to constitute a functional signalling complex with the ubiquitously expressed GM‐CSFRβ subunit, as demonstrated by the fact that GM‐CSF induced the p21‐ras/mitogen‐activated protein kinase (MAPK) signalling cascade in malignant plasma cell lines. Since this signalling cascade plays an essential role in the mediation of both proliferation and cell survival, we investigated the impact of GM‐CSF on these two events. Application of GM‐CSF led to an increase of DNA‐synthesis in MC/CAR, IM‐9 and RPMI‐8226 cells. Furthermore, it increased longevity of these malignant plasma cell lines by reducing the rates of spontaneous apoptosis. We conclude that (i) the functional GM‐CSFR is commonly expressed on malignant plasma cells and that (ii) GM‐CSF promotes the clonal expansion of myeloma cells by inhibiting spontaneous apoptosis and promoting DNA synthesis.</jats:p>
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author Villunger, Andreas, Egle, Alexander, Kos, Marion, Egle, Daniel, Tinhofer, Inge, Henn, Traudl, Überall, Florian, Maly, Karl, Greil, Richard
author_facet Villunger, Andreas, Egle, Alexander, Kos, Marion, Egle, Daniel, Tinhofer, Inge, Henn, Traudl, Überall, Florian, Maly, Karl, Greil, Richard, Villunger, Andreas, Egle, Alexander, Kos, Marion, Egle, Daniel, Tinhofer, Inge, Henn, Traudl, Überall, Florian, Maly, Karl, Greil, Richard
author_sort villunger, andreas
container_issue 4
container_start_page 1069
container_title British Journal of Haematology
container_volume 102
description <jats:p>It has been shown that granulocyte/macrophage colony stimulating factor (GM‐CSF) is able to support myeloma cell propagation in cooperation with interleukin (IL)‐6, the major growth factor for malignant plasma cells, although the biological mechanisms involved remain unknown. Therefore we investigated (i) the expression levels of the GM‐CSF receptor (GM‐CSFR) constituents in three malignant plasma cell lines and in native malignant plasma cells, (ii) the ability of the receptor to mediate common signalling pathways regulating proliferation and cell survival in malignant plasma cell lines, and (iii) the effects of GM‐CSF on tumour cell biology.</jats:p><jats:p>The GM‐CSFRα subunit was detected in the malignant plasma cell lines RPMI‐8226, MC/CAR, IM‐9 as well as 6/6 native myeloma cell samples derived from the bone marrow of patients with overt disease. Furthermore, GM‐CSFR expression was also detected in the CD19<jats:sup>+</jats:sup> fraction from 2/3 bone marrow samples and 5/8 peripheral blood samples derived from patients with malignant plasma cell disorders, but not in the CD19<jats:sup>+</jats:sup> fraction of peripheral blood from healthy donors. The expressed cytokine receptor α‐subunit was able to constitute a functional signalling complex with the ubiquitously expressed GM‐CSFRβ subunit, as demonstrated by the fact that GM‐CSF induced the p21‐ras/mitogen‐activated protein kinase (MAPK) signalling cascade in malignant plasma cell lines. Since this signalling cascade plays an essential role in the mediation of both proliferation and cell survival, we investigated the impact of GM‐CSF on these two events. Application of GM‐CSF led to an increase of DNA‐synthesis in MC/CAR, IM‐9 and RPMI‐8226 cells. Furthermore, it increased longevity of these malignant plasma cell lines by reducing the rates of spontaneous apoptosis. We conclude that (i) the functional GM‐CSFR is commonly expressed on malignant plasma cells and that (ii) GM‐CSF promotes the clonal expansion of myeloma cells by inhibiting spontaneous apoptosis and promoting DNA synthesis.</jats:p>
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spelling Villunger, Andreas Egle, Alexander Kos, Marion Egle, Daniel Tinhofer, Inge Henn, Traudl Überall, Florian Maly, Karl Greil, Richard 0007-1048 1365-2141 Wiley Hematology http://dx.doi.org/10.1046/j.1365-2141.1998.00880.x <jats:p>It has been shown that granulocyte/macrophage colony stimulating factor (GM‐CSF) is able to support myeloma cell propagation in cooperation with interleukin (IL)‐6, the major growth factor for malignant plasma cells, although the biological mechanisms involved remain unknown. Therefore we investigated (i) the expression levels of the GM‐CSF receptor (GM‐CSFR) constituents in three malignant plasma cell lines and in native malignant plasma cells, (ii) the ability of the receptor to mediate common signalling pathways regulating proliferation and cell survival in malignant plasma cell lines, and (iii) the effects of GM‐CSF on tumour cell biology.</jats:p><jats:p>The GM‐CSFRα subunit was detected in the malignant plasma cell lines RPMI‐8226, MC/CAR, IM‐9 as well as 6/6 native myeloma cell samples derived from the bone marrow of patients with overt disease. Furthermore, GM‐CSFR expression was also detected in the CD19<jats:sup>+</jats:sup> fraction from 2/3 bone marrow samples and 5/8 peripheral blood samples derived from patients with malignant plasma cell disorders, but not in the CD19<jats:sup>+</jats:sup> fraction of peripheral blood from healthy donors. The expressed cytokine receptor α‐subunit was able to constitute a functional signalling complex with the ubiquitously expressed GM‐CSFRβ subunit, as demonstrated by the fact that GM‐CSF induced the p21‐ras/mitogen‐activated protein kinase (MAPK) signalling cascade in malignant plasma cell lines. Since this signalling cascade plays an essential role in the mediation of both proliferation and cell survival, we investigated the impact of GM‐CSF on these two events. Application of GM‐CSF led to an increase of DNA‐synthesis in MC/CAR, IM‐9 and RPMI‐8226 cells. Furthermore, it increased longevity of these malignant plasma cell lines by reducing the rates of spontaneous apoptosis. We conclude that (i) the functional GM‐CSFR is commonly expressed on malignant plasma cells and that (ii) GM‐CSF promotes the clonal expansion of myeloma cells by inhibiting spontaneous apoptosis and promoting DNA synthesis.</jats:p> Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity British Journal of Haematology
spellingShingle Villunger, Andreas, Egle, Alexander, Kos, Marion, Egle, Daniel, Tinhofer, Inge, Henn, Traudl, Überall, Florian, Maly, Karl, Greil, Richard, British Journal of Haematology, Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity, Hematology
title Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_full Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_fullStr Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_full_unstemmed Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_short Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_sort functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
title_unstemmed Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity
topic Hematology
url http://dx.doi.org/10.1046/j.1365-2141.1998.00880.x