scholarly journals Gangliosides of myelosupportive stroma cells are transferred to myeloid progenitors and are required for their survival and proliferation

2006 ◽  
Vol 394 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Ana L. Ziulkoski ◽  
Cláudia M. B. Andrade ◽  
Pilar M. Crespo ◽  
Elisa Sisti ◽  
Vera M. T. Trindade ◽  
...  
Keyword(s):  
Growth Factors ◽  
Heparan Sulphate ◽  
Myeloid Cells ◽  
Target Cells ◽  
Reporter System ◽  
Gm Csf ◽  
Heparan Sulphate Proteoglycans ◽  
Α Chain ◽  
Major Ganglioside ◽  
Myeloid Progenitors

In previous studies, we have shown that the myelopoiesis dependent upon myelosupportive stroma required production of growth factors and heparan-sulphate proteoglycans, as well as generation of a negatively charged sialidase-sensitive intercellular environment between the stroma and the myeloid progenitors. In the present study, we have investigated the production, distribution and role of gangliosides in an experimental model of in vitro myelopoiesis dependent upon AFT-024 murine liver-derived stroma. We used the FDC-P1 cell line, which is dependent upon GM-CSF (granulocyte/macrophage colony-stimulating factor) for both survival and proliferation, as a reporter system to monitor bioavailability and local activity of GM-CSF. GM3 was the major ganglioside produced by stroma, but not by myeloid cells, and it was required for optimal stroma myelosupportive function. It was released into the supernatant and selectively incorporated into the myeloid progenitor cells, where it segregated into rafts in which it co-localized with the GM-CSF-receptor α chain. This ganglioside was also metabolized further by myeloid cells into gangliosides of the a and b series, similar to endogenous GM3. In these cells, GM1 was the major ganglioside and it was segregated at the interface by stroma and myeloid cells, partially co-localizing with the GM-CSF-receptor α chain. We conclude that myelosupportive stroma cells produce and secrete the required growth factors, the cofactors such as heparan sulphate proteoglycans, and also supply gangliosides that are transferred from stroma to target cells, generating on the latter ones specific membrane domains with molecular complexes that include growth factor receptors.

Cell membrane-associated proteoglycans mediate extramedullar myeloid proliferation in granulomatous inflammatory reactions to schistosome eggs

1993 ◽  
Vol 104 (2) ◽  
pp. 477-484
Author(s):  
M. Alvarez-Silva ◽  
L.C. da Silva ◽  
R. Borojevic
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Connective Tissue ◽  
Endogenous Growth ◽  
Cell Lines ◽  
Cell Layer ◽  
Heparan Sulphate ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Gm Csf

In chronic murine schistosomiasis, extramedullar myelopoiesis was observed, with proliferation of myeloid cells in liver parenchyma and in periovular granulomas. We have studied the question of whether cells obtained from granulomatous connective tissue may act as myelopoietic stroma, supporting long-term myeloid proliferation. Primary cell lines (GR) were obtained in vitro from periovular granulomas, induced in mouse livers by Schistosoma mansoni infection. These cells were characterized as myofibroblasts, and represent liver connective tissue cells involved in fibro-granulomatous reactions. They were able to sustain survival and proliferation of the multipotent myeloid cell lines FDC-P1 and DA-1 (dependent on interleukin-3 and/or granulocyte-macrophage colony stimulating factor, GM-CSF) without the addition of exogenous growth factors. This stimulation was dependent upon myeloid cell attachment to the GR cell layer; GR cell-conditioned medium had no activity. Primary murine skin fibroblasts could not sustain myelopoiesis. The endogenous growth-factor was identified as GM-CSF by neutralization assays with monoclonal antibodies. The stimulation of myelopoiesis occurred also when GR cells had been fixed with glutardialdehyde. The observed stimulatory activity was dependent upon heparan sulphate proteoglycans (HSPGs) associated with GR cell membranes. It could be dislodged from the cell layer with heparin or a high salt buffer. Our results indicate a molecular interaction between endogenous growth-factor and HSPGs; this interaction may be responsible for the stabilization and presentation of growth factors in myelopoietic stromas, mediating extramedullar proliferation of myeloid cells in periovular granulomas.

118. CHARACTERISATION OF HEPARAN SULPHATE PROTEOGLYCANS IN THE MATURING CUMULUS OOCYTE COMPLEX

2009 ◽  
Vol 21 (9) ◽  
pp. 37
Author(s):  
L. N. Watson ◽  
M. Sasseville ◽  
R. B. Gilchrist ◽  
D. L. Russell
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Surface ◽  
Transforming Growth Factor ◽  
Heparan Sulphate ◽  
Cumulus Cells ◽  
Receptor Interaction ◽  
Heparan Sulphate Proteoglycans ◽  
Tgfβ Superfamily

Many growth factors including members of the transforming growth factor beta (TGFβ) superfamily and epidermal growth factor (Egf)-like ligands signal via interactions with heparan sulphate proteoglycans (HSPGs). Cell surface HSPGs can act by sequestering ligands at their site of action, by presenting a ligand to its signalling receptor, or by preventing ligand-receptor interaction. The oocyte secreted factors (OSF) growth differentiation factor 9 and bone morphogenetic protein 15 are members of the TGFβ superfamily that act selectively on cumulus cells. Conversely Egf-like ligands are secreted by mural granulosa cells and transmit LH-induced signals to cumulus cells. We investigated the possibility that HSPGs contribute to the spatially restricted responses these signals exert on cumulus cells. Syndecan-1 and Glypican-1 are cell surface HSPGs that are involved in numerous biological processes, including growth factor regulation, cell proliferation and differentiation. Microarray analysis showed Syndecan-1 and Glypican-1 mRNA expression induced 6-fold (P=10-9) and 3-fold (P=10-7) respectively in Egf+FSH stimulated cumulus oocyte complexes (COCs). Furthermore, Syndecan-1 and Glypican-1 mRNA were induced 27- and 16-fold respectively in COCs after hCG treatment of mice. Syndecan-1 and Glypican-1 protein was localised specifically to the COC through immunohistochemical analysis. In Vitro Maturation (IVM) of oocytes is a valuable alternative to gonadotropin mediated superovulation, but IVM COCs are less competent than those matured in vivo. Several components of the COC have been shown to be altered in IVM, including the chondroitin sulphate proteoglycan Versican. COCs from mice that underwent IVM in the presence of Egf+FSH and cilostamide for 16 hours had >16 fold reduced mRNA for Syndecan-1 when compared with In Vivo matured COCs. The lack of Syndecan-1 in IVM COCs could reduce signalling capacity of growth factors including OSFs. This may contribute to the reduced capacity of IVM oocytes to fertilise and produce a healthy embryo, and ultimately, a healthy offspring.

scholarly journals Murine myeloid cells transformed by myb require fibroblast-derived or autocrine growth factors in addition to granulocyte-macrophage colony- stimulating factor for proliferation

Blood ◽  
1994 ◽  
Vol 83 (1) ◽  
pp. 209-216 ◽  
Author(s):  
EM Macmillan ◽  
TJ Gonda
Keyword(s):  
Growth Factors ◽  
Myeloid Cells ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Autocrine Growth ◽  
Gm Csf ◽  
Absolute Dependence ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Murine myeloid cells can be transformed in vitro by infection with recombinant retroviruses carrying activated myb genes. While these myb- transformed hematopoietic cells (MTHCs) can proliferate continuously in culture, they exhibit several characteristics of progenitor cells of the granulocyte-macrophage (GM) lineage, including an absolute dependence on hematopoietic growth factors (HGFs) such as GM colony- stimulating factor (GM-CSF) for survival and growth. Whereas we have previously shown that MTHCs respond synergistically to certain combinations of HGFs, we report here that MTHCs apparently require two HGFs for proliferation, because GM-CSF alone appears insufficient to promote growth when MTHCs are cultured at very low densities. However, proliferation can be stimulated by either increasing the density at which MTHCs are cultured (implying the production of an autocrine growth factor) or by the presence of a feeder layer of irradiated fibroblasts. We find that the activity of such feeder layers is greatest when the MTHCs are allowed to contact them directly; and by using mutant fibroblast lines, that it depends on the production of CSF- 1, but not Steel factor (SLF). In contrast, the autocrine factor appears not to be either CSF-1 or SLF, and the possibility is raised that it may represent a novel HGF activity. Potential implications of these results for normal and leukemic hematopoiesis are discussed.

scholarly journals A novel role for syndecan-3 in angiogenesis

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 270 ◽  
Author(s):  
Giulia De Rossi ◽  
James R. Whiteford
Keyword(s):  
Cell Migration ◽  
Growth Factors ◽  
Endothelial Cell ◽  
Heparan Sulphate ◽  
Endothelial Cell Migration ◽  
Regulatory Motifs ◽  
Angiogenic Therapy ◽  
Core Proteins ◽  
Gst Fusion Protein ◽  
Heparan Sulphate Proteoglycans

Syndecan-3 is one of the four members of the syndecan family of heparan sulphate proteoglycans and has been shown to interact with numerous growth factors via its heparan sulphate chains. The extracellular core proteins of syndecan-1,-2 and -4 all possess adhesion regulatory motifs and we hypothesized that syndecan-3 may also possess such characteristics. Here we show that a bacterially expressed GST fusion protein consisting of the entire mature syndecan-3 ectodomain has anti-angiogenic properties and acts via modulating endothelial cell migration. This work identifies syndecan-3 as a possible therapeutic target for anti-angiogenic therapy.

scholarly journals Effects of the stem cell factor, c-kit ligand, on human megakaryocytic cells

Blood ◽  
1992 ◽  
Vol 79 (2) ◽  
pp. 365-371 ◽  
Author(s):  
H Avraham ◽  
E Vannier ◽  
S Cowley ◽  
SX Jiang ◽  
S Chi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Growth Factors ◽  
Cell Lines ◽  
Stem Cell Factor ◽  
Target Cells ◽  
Gm Csf ◽  
Kit Ligand ◽  
Factor C ◽  
Megakaryocytic Cell

Abstract The kit ligand (KL), also termed stem cell factor (SCF), is a recently discovered hematopoietic growth factor that augments response of early progenitor cells to other growth factors and supports proliferation of continuous mast cell lines. Histological studies suggest that the receptor for SCF/KL, the c-kit proto-oncogene product, is present in bone marrow megakaryocytes. We studied the effects of SCF/KL on immortalized human megakaryocytic cell lines (CMK, CMK6, and CMK11–5) and on isolated human marrow megakaryocytes. Human SCF/KL alone or in combination with the hematopoietic growth factors, interleukin-3 (IL- 3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL- 6, stimulated proliferation of these megakaryocytic cell lines. SCF/KL treatment did not alter expression of gpIb, gpIIb/IIIa, LFA-1, ICAM-1, or GMP-140 in CMK cells. No effect on ploidy was observed. Furthermore, human SCF/KL induced expression of IL-1 alpha, IL-1 beta, IL-2, and IL- 6 in CMK cells. In a fibrin clot system, SCF/KL modestly potentiated megakaryocyte colony formation when added alone to cultures containing CD34+, DR+ bone marrow cells. Addition of SCF/KL with IL-3 or GM-CSF to these cultures resulted in a more marked marrow megakaryocytic cells. SCF/KL may directly affect megakaryocytopoiesis, as well as secondarily modulate hematopoiesis through induction of cytokines in target cells.

scholarly journals Murine myeloid cells transformed by myb require fibroblast-derived or autocrine growth factors in addition to granulocyte-macrophage colony- stimulating factor for proliferation

Blood ◽  
1994 ◽  
Vol 83 (1) ◽  
pp. 209-216 ◽  
Author(s):  
EM Macmillan ◽  
TJ Gonda
Keyword(s):  
Growth Factors ◽  
Myeloid Cells ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Autocrine Growth ◽  
Gm Csf ◽  
Absolute Dependence ◽  
Macrophage Colony ◽  
Stimulating Factor

Murine myeloid cells can be transformed in vitro by infection with recombinant retroviruses carrying activated myb genes. While these myb- transformed hematopoietic cells (MTHCs) can proliferate continuously in culture, they exhibit several characteristics of progenitor cells of the granulocyte-macrophage (GM) lineage, including an absolute dependence on hematopoietic growth factors (HGFs) such as GM colony- stimulating factor (GM-CSF) for survival and growth. Whereas we have previously shown that MTHCs respond synergistically to certain combinations of HGFs, we report here that MTHCs apparently require two HGFs for proliferation, because GM-CSF alone appears insufficient to promote growth when MTHCs are cultured at very low densities. However, proliferation can be stimulated by either increasing the density at which MTHCs are cultured (implying the production of an autocrine growth factor) or by the presence of a feeder layer of irradiated fibroblasts. We find that the activity of such feeder layers is greatest when the MTHCs are allowed to contact them directly; and by using mutant fibroblast lines, that it depends on the production of CSF- 1, but not Steel factor (SLF). In contrast, the autocrine factor appears not to be either CSF-1 or SLF, and the possibility is raised that it may represent a novel HGF activity. Potential implications of these results for normal and leukemic hematopoiesis are discussed.

scholarly journals Activities of four purified growth factors on highly enriched human hematopoietic progenitor cells

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1508-1523 ◽  
Author(s):  
A Strife ◽  
C Lambek ◽  
D Wisniewski ◽  
S Gulati ◽  
JC Gasson ◽  
...  
Keyword(s):  
Growth Factors ◽  
Progenitor Cells ◽  
Human Growth ◽  
Positive Control ◽  
Velocity Sedimentation ◽  
Target Cells ◽  
Detectable Activity ◽  
Gm Csf ◽  
Macrophage Colony

Abstract The activities of four purified human growth factors: biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor (GM- CSF); recombinant erythroid-potentiating activity (EPA); natural and recombinant pluripoietin (Ppo); and natural pluripoietin alpha (Ppo alpha), were compared on the growth of hematopoietic colonies from enriched populations of human marrow and blood progenitor cells. Conditioned medium from the Mo T cell line (MoCM) was used as a standard positive control. We found that activities of GM-CSF and Ppo alpha on the growth of hematopoietic colonies were indistinguishable; Ppo alpha is now believed to be identical to GM-CSF. Both factors were able to promote the growth of colonies derived from subpopulations of CFU-GM, BFU-E, and CFU-GEM. Colonies derived from CFU-GM and CFU-GEM in cultures stimulated by GM-CSF and Ppo alpha were much smaller than in cultures stimulated by MoCM. In contrast to previous reports in which less highly enriched progenitors were used as target cells, Ppo had no detectable activity on the growth of colonies derived from BFU-E or CFU- GEM but promoted the growth of a subpopulation of CFU-GM derived colonies. Ppo is now recognized to be identical to G-CSF. The GM colonies in cultures stimulated by G-CSF (Ppo) were much smaller than in cultures stimulated by MoCM. EPA had no detectable activity on either the size or number of colonies derived from CFU-GM, BFU-E, or CFU-GEM. Results from experiments using target cell populations of marrow fractions separated by velocity sedimentation and marrow populations following freezing suggested that GM-CSF (Ppo alpha) and G- CSF (Ppo) primarily affect the growth of relatively mature subpopulations of progenitor cells. It is clear from these results that additional factor(s) are present in MoCM that are necessary to stimulate CFU-GM, BFU-E, and CFU-GEM maximally in vitro.

scholarly journals Effects of the stem cell factor, c-kit ligand, on human megakaryocytic cells

Blood ◽  
1992 ◽  
Vol 79 (2) ◽  
pp. 365-371 ◽  
Author(s):  
H Avraham ◽  
E Vannier ◽  
S Cowley ◽  
SX Jiang ◽  
S Chi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Growth Factors ◽  
Cell Lines ◽  
Stem Cell Factor ◽  
Target Cells ◽  
Gm Csf ◽  
Kit Ligand ◽  
Factor C ◽  
Megakaryocytic Cell

The kit ligand (KL), also termed stem cell factor (SCF), is a recently discovered hematopoietic growth factor that augments response of early progenitor cells to other growth factors and supports proliferation of continuous mast cell lines. Histological studies suggest that the receptor for SCF/KL, the c-kit proto-oncogene product, is present in bone marrow megakaryocytes. We studied the effects of SCF/KL on immortalized human megakaryocytic cell lines (CMK, CMK6, and CMK11–5) and on isolated human marrow megakaryocytes. Human SCF/KL alone or in combination with the hematopoietic growth factors, interleukin-3 (IL- 3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL- 6, stimulated proliferation of these megakaryocytic cell lines. SCF/KL treatment did not alter expression of gpIb, gpIIb/IIIa, LFA-1, ICAM-1, or GMP-140 in CMK cells. No effect on ploidy was observed. Furthermore, human SCF/KL induced expression of IL-1 alpha, IL-1 beta, IL-2, and IL- 6 in CMK cells. In a fibrin clot system, SCF/KL modestly potentiated megakaryocyte colony formation when added alone to cultures containing CD34+, DR+ bone marrow cells. Addition of SCF/KL with IL-3 or GM-CSF to these cultures resulted in a more marked marrow megakaryocytic cells. SCF/KL may directly affect megakaryocytopoiesis, as well as secondarily modulate hematopoiesis through induction of cytokines in target cells.

Fibroblast growth factors and their receptors

1997 ◽  
Vol 75 (6) ◽  
pp. 669-685 ◽  
Author(s):  
Zoya Galzie ◽  
Anne R Kinsella ◽  
John A Smith
Keyword(s):  
Growth Factors ◽  
Heparan Sulphate ◽  
Fibroblast Growth Factors ◽  
Biological Properties ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Surface Receptors ◽  
Normal Tissues ◽  
Tumour Diagnosis ◽  
Heparan Sulphate Proteoglycans

Fibroblast growth factors (FGFs) represent a group of polypeptide mitogens eliciting a wide variety of responses depending upon the target cell type. The knowledge of the cell surface receptors mediating the effects of FGFs has recently expanded remarkably. The complexity of the FGF family and the FGF-induced responses is reflected in the diversity and redundancy of the FGF receptors. In this review, a number of biochemical characteristics and biological properties of the FGF family and its receptors are described and their expression both in normal tissues and in tumours is discussed. Finally we speculate on the targetting of growth inhibition agents to tumours through FGF receptors. Key words: fibroblast growth factor, FGF receptor, heparan sulphate proteoglycans, tyrosine kinase receptors, FGF in tumour diagnosis.

scholarly journals Fibroblast growth factors share binding sites in heparan sulphate

2005 ◽  
Vol 389 (1) ◽  
pp. 145-150 ◽  
Author(s):  
Johan KREUGER ◽  
Per JEMTH ◽  
Emil SANDERS-LINDBERG ◽  
Liat ELIAHU ◽  
Dina RON ◽  
...  
Keyword(s):  
Growth Factors ◽  
Sequence Analysis ◽  
Binding Sites ◽  
Heparan Sulphate ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Cellular Targeting ◽  
Selective Modulation ◽  
Comprehensive Survey ◽  
Heparan Sulphate Proteoglycans

HS (heparan sulphate) proteoglycans bind secreted signalling proteins, including FGFs (fibroblast growth factors) through their HS side chains. Such chains contain a wealth of differentially sulphated saccharide epitopes. Whereas specific HS structures are commonly believed to modulate FGF-binding and activity, selective binding of defined HS epitopes to FGFs has generally not been demonstrated. In the present paper, we have identified a series of sulphated HS octasaccharide epitopes, derived from authentic HS or from biosynthetic libraries that bind with graded affinities to FGF4, FGF7 and FGF8b. These HS species, along with previously identified oligosaccharides that interact with FGF1 and FGF2, constitute the first comprehensive survey of FGF-binding HS epitopes based on carbohydrate sequence analysis. Unexpectedly, our results demonstrate that selective modulation of FGF activity cannot be explained in terms of binding of individual FGFs to specific HS target epitopes. Instead, different FGFs bind to identical HS epitopes with similar relative affinities and low selectivity, such that the strength of these interactions increases with increasing saccharide charge density. We conclude that FGFs show extensive sharing of binding sites in HS. This conclusion challenges the current notion of specificity in HS–FGF interactions, and instead suggests that a set of common HS motifs mediates cellular targeting of different FGFs.

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