A clinical role for stem cell factor (SCF) in cancer patient management

1997 ◽  
Vol 33 ◽  
pp. S11
Author(s):  
D Crowther ◽  
A Weaver
Keyword(s):  
Stem Cell ◽  
Cancer Patient ◽  
Stem Cell Factor ◽  
Patient Management ◽  
Clinical Role

scholarly journals Recombinant human stem cell factor, a c-kit ligand, stimulates hematopoiesis in primates

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1975-1980 ◽  
Author(s):  
RG Andrews ◽  
GH Knitter ◽  
SH Bartelmez ◽  
KE Langley ◽  
D Farrar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Absolute Number ◽  
Human Stem Cell ◽  
Clinical Role ◽  
Gm Csf ◽  
Macrophage Colony ◽  
Human Stem Cell Factor

Abstract Recombinant human stem cell factor (SCF) is homologous with recombinant rat SCF (rrSCF) and is a ligand for c-kit. We determined the influence of SCF on hematopoiesis in vitro and in vivo in baboons. In vitro, SCF alone stimulated little growth of hematopoietic colony-forming cells from baboon marrow, but did increase the number of colonies formed in response to erythropoietin (Epo), interleukin-3 (IL-3), and granulocyte- macrophage colony-stimulating factor (GM-CSF). In vivo, SCF caused an increase in the peripheral blood of the number of erythrocytes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. In marrow, it caused an increase in marrow cellularity and in the absolute number of colony-forming unit-granulocyte-monocyte (CFU-GM) and burst- forming unit-erythroid (BFU-E) in marrow following infusion of SCF. The in vivo stimulation of multiple lymphohematopoietic lineages corroborates previous in vitro studies and suggests a potentially important clinical role for SCF.

scholarly journals The effects on hematopoiesis of recombinant stem cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination with granulocyte colony-stimulating factor

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 961-966 ◽  
Author(s):  
G Molineux ◽  
A Migdalska ◽  
M Szmitkowski ◽  
K Zsebo ◽  
TM Dexter
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Dose Range ◽  
Macrocytic Anemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Clinical Role ◽  
Blood Neutrophils ◽  
Stimulating Factor

Abstract Stem cell factor (SCF) is the ligand for the receptor encoded by the c- kit proto-oncogene. Mutations of either c-kit or the SCF gene are responsible for the defects of W and SI mutant mice, which both suffer a macrocytic anemia, the former associated with defective stem cells and the latter with a defective hematopoietic microenvironment. PEGylated recombinant rat SCF was administered to normal or splenectomized mice for up to 21 days. SCF was found to be a modest stimulator of peripheral blood neutrophil numbers in both groups of animals. The peak in neutrophil numbers was higher and occurred earlier in splenectomized mice. Bone marrow and spleen cellularity changed little during treatment but the content of interleukin-3-responsive progenitor cells and spleen colony-forming cells (CFU-S) reached very high levels, particularly in the spleen. Using recombinant human granulocyte colony-stimulating factor (rhG-CSF), we have shown that SCF induces a greater than additive increase in both blood neutrophils and blood-borne CFU-S. This synergy was seen throughout the dose range and may indicate a clinical role for SCF either alone or in augmenting the activity of G-CSF upon blood neutrophils and transplantable stem cells.

scholarly journals Recombinant human stem cell factor, a c-kit ligand, stimulates hematopoiesis in primates

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1975-1980 ◽  
Author(s):  
RG Andrews ◽  
GH Knitter ◽  
SH Bartelmez ◽  
KE Langley ◽  
D Farrar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Absolute Number ◽  
Human Stem Cell ◽  
Clinical Role ◽  
Gm Csf ◽  
Macrophage Colony ◽  
Human Stem Cell Factor

Recombinant human stem cell factor (SCF) is homologous with recombinant rat SCF (rrSCF) and is a ligand for c-kit. We determined the influence of SCF on hematopoiesis in vitro and in vivo in baboons. In vitro, SCF alone stimulated little growth of hematopoietic colony-forming cells from baboon marrow, but did increase the number of colonies formed in response to erythropoietin (Epo), interleukin-3 (IL-3), and granulocyte- macrophage colony-stimulating factor (GM-CSF). In vivo, SCF caused an increase in the peripheral blood of the number of erythrocytes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. In marrow, it caused an increase in marrow cellularity and in the absolute number of colony-forming unit-granulocyte-monocyte (CFU-GM) and burst- forming unit-erythroid (BFU-E) in marrow following infusion of SCF. The in vivo stimulation of multiple lymphohematopoietic lineages corroborates previous in vitro studies and suggests a potentially important clinical role for SCF.

scholarly journals The effects on hematopoiesis of recombinant stem cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination with granulocyte colony-stimulating factor

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 961-966 ◽  
Author(s):  
G Molineux ◽  
A Migdalska ◽  
M Szmitkowski ◽  
K Zsebo ◽  
TM Dexter
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Dose Range ◽  
Macrocytic Anemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Clinical Role ◽  
Blood Neutrophils ◽  
Stimulating Factor

Stem cell factor (SCF) is the ligand for the receptor encoded by the c- kit proto-oncogene. Mutations of either c-kit or the SCF gene are responsible for the defects of W and SI mutant mice, which both suffer a macrocytic anemia, the former associated with defective stem cells and the latter with a defective hematopoietic microenvironment. PEGylated recombinant rat SCF was administered to normal or splenectomized mice for up to 21 days. SCF was found to be a modest stimulator of peripheral blood neutrophil numbers in both groups of animals. The peak in neutrophil numbers was higher and occurred earlier in splenectomized mice. Bone marrow and spleen cellularity changed little during treatment but the content of interleukin-3-responsive progenitor cells and spleen colony-forming cells (CFU-S) reached very high levels, particularly in the spleen. Using recombinant human granulocyte colony-stimulating factor (rhG-CSF), we have shown that SCF induces a greater than additive increase in both blood neutrophils and blood-borne CFU-S. This synergy was seen throughout the dose range and may indicate a clinical role for SCF either alone or in augmenting the activity of G-CSF upon blood neutrophils and transplantable stem cells.

Stem Cell Factor

2002 ◽  
Vol 14 (2) ◽  
pp. 0052-0059 ◽  
Author(s):  
Susan Smith ◽  
Adrian Piliponsky ◽  
Mor-Li Hartman ◽  
Francesca Levi-Schaffer
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor

Downregulation of c-kit (Stem Cell Factor Receptor) in Transformed Hematopoietic Precursor Cells by Stroma Cells

Blood ◽  
1999 ◽  
Vol 93 (2) ◽  
pp. 554-563 ◽  
Author(s):  
Christoph Heberlein ◽  
Jutta Friel ◽  
Christine Laker ◽  
Dorothee von Laer ◽  
Ulla Bergholz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Line ◽  
Stem Cell Factor ◽  
Progenitor Cell ◽  
Receptor Expression ◽  
General Mechanism ◽  
Ligand Interaction ◽  
Kit Ligand ◽  
Kit Receptor ◽  
Progenitor Cell Line

Abstract We show a dramatic downregulation of the stem cell factor (SCF) receptor in different hematopoietic cell lines by murine stroma. Growth of the human erythroid/macrophage progenitor cell line TF-1 is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3). However, TF-1 cells clone and proliferate equally well on stroma. Independent stroma-dependent TF-1 clones (TF-1S) were generated on MS-5 stroma. Growth of TF-1S and TF-1 cells on stroma still requires interaction between c-kit (SCF receptor) and its ligand SCF, because antibodies against c-kit inhibit growth to less than 2%. Surprisingly, c-kit receptor expression (RNA and protein) was downregulated by 2 to 3 orders of magnitude in TF-1S and TF-1 cells grown on stroma. This stroma-dependent regulation of the kit receptor in TF-1 was also observed on exposure to kit ligand-negative stroma, thus indicating the need for heterologous receptor ligand interaction. Removal of stroma induced upregulation by 2 to 4 orders of magnitude. Downregulation and upregulation of c-kit expression could also be shown for the megakaryocytic progenitor cell line M-07e and was comparable to that of TF-1, indicating that stroma-dependent regulation of c-kit is a general mechanism. Downregulation may be an economic way to compensate for the increased sensitivity of the c-kit/ligand interaction on stroma. The stroma-dependent c-kit regulation most likely occurs at the transcriptional level, because mechanisms, such as splicing, attenuation, differential promoter usage, or mRNA stability, could be excluded.

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