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Titolo:
Effects of vascular endothelial and platelet-derived growth factor receptor inhibitors on long-term cultures from normal human bone marrow
Autore:
Duhrsen, U; Martinez, T; Vohwinkel, G; Ergun, S; Sun, L; McMahon, G; Durig, J; Hossfeld, DK; Fielder, W;
Indirizzi:
Univ Klinikum Essen, Zentrum Innere Med, Hamatol Abt, Essen, Germany Univ Klinikum Essen Essen Germany nere Med, Hamatol Abt, Essen, Germany Univ Hamburg, Krankenhaus Eppendorf, Med Klin, Abt Onkol & Hamatol, Hamburg, Germany Univ Hamburg Hamburg Germany lin, Abt Onkol & Hamatol, Hamburg, Germany Univ Hamburg, Krankenhaus Eppendorf, Inst Anat, Hamburg, Germany Univ Hamburg Hamburg Germany aus Eppendorf, Inst Anat, Hamburg, Germany SUGEN, S San Francisco, CA USA SUGEN S San Francisco CA USASUGEN, S San Francisco, CA USA
Titolo Testata:
GROWTH FACTORS
fascicolo: 1, volume: 19, anno: 2001,
pagine: 1 - 17
SICI:
0897-7194(2001)19:1<1:EOVEAP>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; FACTOR VEGF; HORSERADISH-PEROXIDASE; TYROSINE KINASES; STROMAL CELLS; MICROENVIRONMENT; INVITRO; ANGIOGENESIS; BETA;
Keywords:
haemopoiesis; long-term bone marrow culture; platelet-derived growth factor; tyrosine kinase inhibitor; vascular endothelial growth factor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Duhrsen, U Univ Klinikum Essen, Zentrum Innere Med, Hamatol Abt, Essen, Germany Univ Klinikum Essen Essen Germany amatol Abt, Essen, Germany
Citazione:
U. Duhrsen et al., "Effects of vascular endothelial and platelet-derived growth factor receptor inhibitors on long-term cultures from normal human bone marrow", GROW FACTOR, 19(1), 2001, pp. 1-17

Abstract

Endothelial cells and fibroblasts are important constituents of the haemopoietic microenvironment. Growth and function of these cells are controlled by a variety of cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). We analysed the effects of novel tyrosine kinase inhibitors targeting the VEGF and PDGF receptors (compounds SU5614 and SU5768) on the performance of long-term cultures from normal human bone marrow. In developing cultures, the inhibitors induced a dose-dependent reduction in stromal. fibroblasts, macrophages and endothelial cells with a concomitant decrease in blood cell production and an increase in fat cells. For SU5614, the concentration Whiting stroma formation by 50% (IC50) was 123nM, andthe IC50 for haemopoietic. colony forming cell output was 186 nM. For SU5768, the respective values were 871 nM and 331 nM. Changes in stroma composition and inhibition of haemopoietic cell production were also demonstrable after delayed addition of the inhibitors to established cultures. By contrast, haemopoietic colony formation in clonogenic agar cultures was unimpaired (IC50 not reached at 100 muM). Immunofluorescence studies and time courseanalyses suggested that the primary effect of the inhibitors was interference with the proliferation and function of fibroblasts and endothelial cells which in turn resulted in decreased haemopoiesis and increased adipogenesis. This was associated with decreased levels in conditioned media of granulocyte-macrophage colony-stimulating factor, interleukin-6 and leptin. VEGF and PDGF may play a hitherto underestimated role in the control of blood cell formation. VEGF/PDGF receptor inhibitors may have therapeutic potential in stroma diseases such as myelofibrosis. Since they weaken the stimulatory signals provided by the microenvironment, they may also be of value in the treatment of leukaemia and other neoplastic bone marrow diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 23:06:33