scholarly journals Exon switching and activation of stromal and embryonic fibroblast growth factor (FGF)-FGF receptor genes in prostate epithelial cells accompany stromal independence and malignancy.

1993 ◽  
Vol 13 (8) ◽  
pp. 4513-4522 ◽  
Author(s):  
G Yan ◽  
Y Fukabori ◽  
G McBride ◽  
S Nikolaropolous ◽  
W L McKeehan
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Fibroblast Growth Factor ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Malignant Tumors ◽  
Family Influence ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
High Affinity

Stroma and the heparin-binding fibroblast growth factor (FGF) family influence normal epithelial cell growth and differentiation in embryonic and adult tissues. The role of stromal cells and the expression of isoforms of the FGF ligand and receptor family were examined during malignant progression of epithelial cells from a differentiated, slowly growing, nonmalignant model rat prostate tumor. In syngeneic hosts, a mixture of stromal and epithelial cells resulted in nonmalignant tumors which were differentiated and slowly growing. In the absence of the stromal cells, epithelial cells progressed to malignant tumors which were independent of the stroma and undifferentiated. The independence of the malignant epithelial cells from stromal cells was accompanied by a switch from exclusive expression of exon IIIb to exclusive expression of exon IIIc in the FGF receptor 2 (FGF-R2) gene. The FGF-R2(IIIb) isoform displays high affinity for stromal cell-derived FGF-7, whereas the FGF-R2(IIIc) isoform does not recognize FGF-7 but has high affinity for the FGF-2 member of the FGF ligand family. The switch from expression of exclusively exon IIIb to exclusively exon IIIc in the resident FGF-R2 gene was followed by activation of the FGF-2 ligand gene, the normally stromal cell FGF-R1 gene, and embryonic FGF-3 and FGF-5 ligand genes in malignant epithelial cells. Multiple autocrine and potentially intracrine ligand-receptor loops resulting from these alterations within the FGF-FGF-R family may underlie the autonomy of malignant tumor cells.

scholarly journals Exon switching and activation of stromal and embryonic fibroblast growth factor (FGF)-FGF receptor genes in prostate epithelial cells accompany stromal independence and malignancy

1993 ◽  
Vol 13 (8) ◽  
pp. 4513-4522
Author(s):  
G Yan ◽  
Y Fukabori ◽  
G McBride ◽  
S Nikolaropolous ◽  
W L McKeehan
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Fibroblast Growth Factor ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Malignant Tumors ◽  
Family Influence ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
High Affinity

Stroma and the heparin-binding fibroblast growth factor (FGF) family influence normal epithelial cell growth and differentiation in embryonic and adult tissues. The role of stromal cells and the expression of isoforms of the FGF ligand and receptor family were examined during malignant progression of epithelial cells from a differentiated, slowly growing, nonmalignant model rat prostate tumor. In syngeneic hosts, a mixture of stromal and epithelial cells resulted in nonmalignant tumors which were differentiated and slowly growing. In the absence of the stromal cells, epithelial cells progressed to malignant tumors which were independent of the stroma and undifferentiated. The independence of the malignant epithelial cells from stromal cells was accompanied by a switch from exclusive expression of exon IIIb to exclusive expression of exon IIIc in the FGF receptor 2 (FGF-R2) gene. The FGF-R2(IIIb) isoform displays high affinity for stromal cell-derived FGF-7, whereas the FGF-R2(IIIc) isoform does not recognize FGF-7 but has high affinity for the FGF-2 member of the FGF ligand family. The switch from expression of exclusively exon IIIb to exclusively exon IIIc in the resident FGF-R2 gene was followed by activation of the FGF-2 ligand gene, the normally stromal cell FGF-R1 gene, and embryonic FGF-3 and FGF-5 ligand genes in malignant epithelial cells. Multiple autocrine and potentially intracrine ligand-receptor loops resulting from these alterations within the FGF-FGF-R family may underlie the autonomy of malignant tumor cells.

scholarly journals Basic fibroblast growth factor expression in human bone marrow and peripheral blood cells

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 631-638 ◽  
Author(s):  
G Brunner ◽  
H Nguyen ◽  
J Gabrilove ◽  
DB Rifkin ◽  
EL Wilson
Keyword(s):  
Bone Marrow ◽  
Extracellular Matrix ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Cell Cultures ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Stromal Cell ◽  
Fibroblast Growth

We have shown previously that basic fibroblast growth factor (bFGF) is a mitogen for human bone marrow (BM) stromal cells and that bFGF stimulates myelopoiesis in primary BM cultures. In this article, we demonstrate the presence of bFGF in two cell lineages in human BM and peripheral blood as well as the deposition of bFGF into the extracellular matrix of BM stromal cell cultures. In immunofluorescence experiments on BM and peripheral blood smears, megakaryocytes and platelets stained strongly for bFGF, whereas weaker staining was observed in immature and mature cells of the granulocyte series. The presence of bFGF in platelets was confirmed by enzyme-linked immunosorbent assay as well as by immunoprecipitation followed by immunoblotting. bFGF was synthesized by BM stromal cell cultures and was found either cell associated or localized in the nucleus and the nucleoli, and its location was dependent on the fixation procedure used. Addition of exogenous bFGF to stromal cells showed the presence of extracellular binding molecules for this cytokine. bFGF could be released from these sites by soluble heparin or phosphatidylinositol- specific phospholipase C. This study supports the role of bFGF as a stromal cell mitogen and stimulator of myelopoiesis. The data indicate that the stromal cells produce bFGF and that their extracellular matrix can serve as a reservoir for this growth factor. In addition, the results suggest a possible involvement of bFGF in platelet function as well as in megakaryocytopoiesis.

scholarly journals Fibroblast Growth Factor (FGF) 3 fromXenopus laevis(XFGF3) Binds with High Affinity to FGF Receptor 2

1995 ◽  
Vol 270 (12) ◽  
pp. 6779-6787 ◽  
Author(s):  
Marc Mathieu ◽  
Paul Kiefer ◽  
Ivor Mason ◽  
Clive Dickson
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
High Affinity

Cytokine regulation of fibroblast growth factor receptor 3 IIIb in intestinal epithelial cells

1997 ◽  
Vol 272 (4) ◽  
pp. G885-G893 ◽  
Author(s):  
M. Kanai ◽  
I. Rosenberg ◽  
D. K. Podolsky
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Intestinal Epithelial Cells ◽  
Interleukin 2 ◽  
Intestinal Epithelial ◽  
Fibroblast Growth ◽  
Fgf Receptor

Proliferation and function of the intestinal epithelium is modulated by a range of regulatory peptides, including cytokines and peptide growth factors. To define mechanisms integrating these regulatory systems, the effects of growth factors and cytokines on the expression of the fibroblast growth factor (FGF) receptor 3 (FGFR3) IIIb expressed on intestinal epithelial cells were examined in Caco-2 cells. Regulated expression of FGFR3 IIIb was associated with acquisition of the differentiated state. Keratinocyte growth factor (KGF), a ligand of another member of the FGF receptor family, enhanced expression of FGFR3 IIIb, but acidic FGF, the ligand for FGFR3 IIIb itself, had no effect. Epidermal growth factor and transforming growth factor-beta also markedly enhanced FGFR3 IIIb expression in a different temporal pattern. In addition, FGFR3 IIIb expression was increased 10-fold by the cytokine interleukin-2. These studies demonstrate integration between cytokines and growth factor ligand-receptor systems in intestinal epithelial cells.

scholarly journals Basic fibroblast growth factor expression in human bone marrow and peripheral blood cells

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 631-638 ◽  
Author(s):  
G Brunner ◽  
H Nguyen ◽  
J Gabrilove ◽  
DB Rifkin ◽  
EL Wilson
Keyword(s):  
Bone Marrow ◽  
Extracellular Matrix ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Cell Cultures ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Stromal Cell ◽  
Fibroblast Growth

Abstract We have shown previously that basic fibroblast growth factor (bFGF) is a mitogen for human bone marrow (BM) stromal cells and that bFGF stimulates myelopoiesis in primary BM cultures. In this article, we demonstrate the presence of bFGF in two cell lineages in human BM and peripheral blood as well as the deposition of bFGF into the extracellular matrix of BM stromal cell cultures. In immunofluorescence experiments on BM and peripheral blood smears, megakaryocytes and platelets stained strongly for bFGF, whereas weaker staining was observed in immature and mature cells of the granulocyte series. The presence of bFGF in platelets was confirmed by enzyme-linked immunosorbent assay as well as by immunoprecipitation followed by immunoblotting. bFGF was synthesized by BM stromal cell cultures and was found either cell associated or localized in the nucleus and the nucleoli, and its location was dependent on the fixation procedure used. Addition of exogenous bFGF to stromal cells showed the presence of extracellular binding molecules for this cytokine. bFGF could be released from these sites by soluble heparin or phosphatidylinositol- specific phospholipase C. This study supports the role of bFGF as a stromal cell mitogen and stimulator of myelopoiesis. The data indicate that the stromal cells produce bFGF and that their extracellular matrix can serve as a reservoir for this growth factor. In addition, the results suggest a possible involvement of bFGF in platelet function as well as in megakaryocytopoiesis.

Sign in / Sign up

Export Citation Format

Share Document