Isolation and characterization of a macrophage-derived heparin-binding growth factor.

Besner, Gail E.; Higashiyama, Shigeki; Klagsbrun, Michael

doi:10.1091/mbc.1.11.811

Cited by 176 publications

(140 citation statements)

References 36 publications

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“…Smooth muscle cells were isolated from a 2-3-cm length of pig thoracic aorta using established procedures (17) and maintained in 10% Dulbecco's modified Eagle's medium, 10% fetal bovine serum. BCEC and smooth muscle cell DNA synthesis assays were performed in 48-or 96-well plates essentially as described (18). BCEC DNA synthesis assays were also performed in the presence of 100 g/ml porcine heparin.…”

Section: Growth Factor Characterizationmentioning

confidence: 99%

Purification and Characterization of Novel Heparin-binding Growth Factors in Uterine Secretory Fluids

Brigstock¹,

Steffen²,

Kim³

et al. 1997

Journal of Biological Chemistry

188

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Uterine growth factors are potential effector molecules in embryo growth signaling pathways. Pig uterine luminal flushings contained a heparin-binding growth factor (HBGF) that required 0.8 M NaCl for elution from heparin columns and was termed HBGF-0.8. This factor, which was heat-and acid-labile and of M r 10,000 as assessed by gel filtration, stimulated DNA synthesis in fibroblasts and smooth muscle cells but not endothelial cells. Two forms of HBGF-0.8, termed HBGF-0.8-P1 and HBGF-0.8-P2, exhibited differential heparin-binding properties. SDS-polyacrylamide gel electrophoresis showed that each form of HBGF-0.8 migrated with an apparent M r of 10,000 under reducing conditions. Amino acid sequencing revealed the N-terminal sequence EEN-IKKGKKXIRTPKI for HBGF-0.8-P1 and ENIKKGKKX-IRT for HBGF-0.8-P2. These sequences corresponded, respectively, to residues 247-262 and 248 -259 of the 349-residue predicted primary translation product of porcine connective tissue growth factor (pCTGF). 10-kDa CTGF-mediated fibroblast DNA synthesis was modulated by exogenous heparin, and CTGF-immunoreactive proteins of 10, 16, and 20 kDa were present in unfractionated uterine luminal flushings. These data reveal the identity of a novel growth factor in uterine fluids as a highly truncated form of CTGF and show that the N-terminal two-thirds of the CTGF primary translation product is not required for mitogenic activity or heparin binding.

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Section: Growth Factor Characterizationmentioning

confidence: 99%

Purification and Characterization of Novel Heparin-binding Growth Factors in Uterine Secretory Fluids

Brigstock¹,

Steffen²,

Kim³

et al. 1997

Journal of Biological Chemistry

188

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“…Heparin-binding EGF-like growth factor (HB-EGF) is a 76-86 amino acid glycosylated protein that was originally cloned from macrophage-like U937 cells (25)(26)(27). HB-EGF is an activating ligand for HER1 and a potent mitogen for smooth muscle cells and fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

“…HB-EGF is an activating ligand for HER1 and a potent mitogen for smooth muscle cells and fibroblasts. Soluble HB-EGF appears to be an inflammatory mediator because expression of the HB-EGF gene is rapidly activated by inflammatory cytokines such as TNF ␣ , IL-1 ␤ , PDGF, and basic fibroblast growth factor (bFGF) (28,29) and because HB-EGF is a secreted product of monocyte-derived macrophages and CD4 ϩ T lymphocytes (25,30). HB-EGF is also expressed by macrophages and smooth muscle cells residing in human atherosclerotic plaques (31) and by eosinophils infiltrating lung tissue subsequent to hypoxia (32).…”

Section: Introductionmentioning

confidence: 99%

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Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.

Freeman¹,

et al. 1997

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The epidermal growth factor receptor (HER1) has been implicated in regenerative growth and proliferative diseases of the human bladder epithelium (urothelium), however a cognate HER1 ligand that can act as a growth factor for normal human urothelial cells (HUC) has not been identified. Here we show that heparin-binding EGF-like growth factor (HB-EGF), an activating HER1 ligand, is an autocrine regulator of HUC growth. This conclusion is based on demonstration of HB-EGF synthesis and secretion by primary culture HUC, identification of HER1 as an activatable HB-EGF receptor on HUC surfaces, stimulation of HUC clonal growth by HB-EGF, inhibition of HB-EGF-stimulated growth by heparin and of log-phase growth by CRM 197, a specific inhibitor of HB-EGF/HER1 interaction, and identification of human urothelium as a site of HB-EGF precursor (proHB-EGF) synthesis in vivo. ProHB-EGF expression was also detected in the vascular and detrusor smooth muscle of the human bladder. These data suggest a physiologic role for HB-EGF in the regulation of urothelial proliferation and regeneration subsequent to mucosal injury. Expression of proHB-EGF is also a feature of differentiated vascular and detrusor smooth muscle in the bladder. Because proHB-EGF is known to be the high affinity diphtheria toxin (DT) receptor in human cells, synthesis of the HB-EGF precursor by human urothelium also suggests the possibility of using the DT-binding sites of proHB-EGF as an in vivo target for the intraluminal treatment of urothelial diseases. ( J. Clin. Invest. 1997. 99:1028-1036.)

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“…11,12 When HB-EGF binds to EGF receptors, it induces EGF receptor autophosphorylation, as well as a variety of other biological activities, including proliferation and migration. Secreted mature HB-EGF is a potent mitogen for NIH-3T3 cells, bovine aortic smooth muscle cells (BASMC), [11][12][13] rat hepatocytes, 14 human keratinocytes 15,16 and rat gastric epithelial cells. 17 In addition, in a previous study, we demonstrated that HB-EGF is present in human gastric mucosa.…”

mentioning

confidence: 99%

Significance of the association between heparin‐binding epidermal growth factor‐like growth factor and CD9 in human gastric cancer

Murayama

Miyagawa

Shinomura

et al. 2002

Intl Journal of Cancer

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Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family. Juxtacrine activity of proHB-EGF (the membrane-anchored form of HB-EGF) has been shown to be significantly potentiated when it is coexpressed with CD9 in vitro. The purpose of our study was to investigate the issue of whether proHB-EGF and CD9 are coexpressed in gastric cancer. HB-EGF gene expression and protein production in human gastric cancers was investigated, and EGF receptor and CD9 expressions were also evaluated. HB-EGF mRNA levels in gastric cancers were elevated, compared with normal gastric tissues, especially in the intestinal type. ProHB-EGF immunoreactivity was detected primarily in the cytoplasm and plasma membrane of gastric cancer cells. Of 66 patients, 40 (60.6%) exhibited proHB-EGF immunoreactivity and the level of its expression was significantly associated with tumor status (p < 0.01) and histological differentiation (p < 0.001). In addition, proHB-EGF mRNA was detected at high levels in the intestinal type by in situ hybridization. CD9 immunoreactivity was found to be preserved in 26 of 36 patients (72.2%) and CD9 protein expression was inversely associated with lymph node status (p < 0.05). A significant correlation between its expression and histological differentiation (p < 0.01) was found, and the association of CD9 with proHB-EGF was increased in the intestinal type, as evidenced by an immunoprecipitation method. These results indicate that the coexpression of proHB-EGF and CD9 may be involved in the tumorigenesis and/or proliferation of gastric cancers in a juxtacrine manner.

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Isolation and characterization of a macrophage-derived heparin-binding growth factor.

Cited by 176 publications

References 36 publications

Purification and Characterization of Novel Heparin-binding Growth Factors in Uterine Secretory Fluids

Purification and Characterization of Novel Heparin-binding Growth Factors in Uterine Secretory Fluids

Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.

Significance of the association between heparin‐binding epidermal growth factor‐like growth factor and CD9 in human gastric cancer

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