Partial purification and characterization of human hepatoma-derived growth factor

Nakamura, Hitomi; Kambe, Hiroshi; Egawa, Takako; Kimura, Yuichi; Ito, Hiroaki; Hayashi, Eiji; Yamamoto, Hideo; Sato, Jiro; Kishimoto, Susumu

doi:10.1016/0009-8981(89)90361-6

Cited by 109 publications

(96 citation statements)

References 10 publications

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“…Primary human skin fibroblasts were seeded into 24-well plates at a density of 6,000 cells/cm 2 and cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. After 6 days, medium was replaced by Dulbecco's modified Eagle's medium containing no fetal bovine serum but containing different concentrations of the respective histidine-tagged recombinant proteins or synthetically produced peptides (EMC, Tuebingen, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Hepatoma-derived growth factor (HDGF) 1 was initially purified from the supernatant of human hepatoma cell lines (1)(2)(3).…”

mentioning

confidence: 99%

“…It has been shown to have growth factor activity for hepatoma cells, fibroblasts, smooth muscle cells, and endothelial cells (1,2,4,5). In addition, it has recently been shown to be neurotrophic (6).…”

mentioning

confidence: 99%

“…The nuclear localization has been shown to be a prerequisite for the mitogenic activity of intracellularly expressed HDGF (5,26). Several groups have shown independently that HDGF is mitogenic not only when expressed in cells but also when applied exogenously (2,3). Despite its purification from cell culture medium and its mitogenic properties as an exogenous ligand, HDGF lacks a classical signal sequence and is only poorly secreted by transfected cell lines.…”

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confidence: 99%

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Hepatoma-derived Growth Factor

Abouzied

Eltahir

Prenner

et al. 2005

Journal of Biological Chemistry

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Hepatoma-derived growth factor (HDGF) has proliferative, angiogenic, and neurotrophic activity. It plays a putative role in the development and progression of cancer. When expressed in cells, the mitogenic activity of HDGF depends on its nuclear localization, but it also stimulates proliferation when added to the cell culture medium. A cell surface receptor for HDGF has not been identified so far. We investigated the interaction of various purified recombinant HDGF fusion proteins with the cell surface of NIH 3T3 fibroblasts. We showed that binding of a HDGF-␤-galactosidase fusion protein to the cell surface of NIH 3T3 fibroblasts was saturable, occurred with high affinity (K D ‫؍‬ 14 nM), and had a proliferative effect. We identified a peptide comprising amino acid residues 81-100 within the amino-terminal part of HDGF that bound to the cell surface of NIH 3T3 cells with saturation and affinity values similar to those of HDGF. When added to primary human fibroblasts, this peptide stimulated proliferation. Substitution of a single amino acid (K96A) within this peptide was sufficient to abolish its binding to the cell surface and its proliferative activity. In contrast, when expressed transiently in NIH 3T3 cells, a HDGF-␤-galactosidase fusion protein in which amino acid residues 81-100 were deleted still had proliferative activity, whereas a fusion protein containing only the 81-100 peptide did not. Our results suggest the existence of a plasma membrane-located HDGF receptor for which signaling depends on amino acid residues 81-100 of HDGF. This region differs from the one that has been recently identified to be essential for mitogenic activity depending on the nuclear localization of HDGF. Thus, HDGF exerts its proliferative activity via two different pathways.

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Section: Methodsmentioning

confidence: 99%

“…Hepatoma-derived growth factor (HDGF) 1 was initially purified from the supernatant of human hepatoma cell lines (1)(2)(3).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Hepatoma-derived Growth Factor

Abouzied

Eltahir

Prenner

et al. 2005

Journal of Biological Chemistry

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“…Hepatoma-derived growth factor (HDGF) is a heparinbinding factor originally purified from the culture supernatants of Huh-7 human hepatoma cell line (Cilley et al 2000) and its cDNA was cloned from the cDNA library of HuH-7 cells (Nakamura et al 1989(Nakamura et al , 1994, but its expression is not restricted only in liver or hepatoma. HDGF was reported to be expressed widespread and played important roles in the development, repair and remodeling of various tissues and organs (Oliver and Al-Awqati 1998;Lepourcelet et al 2005;Narron et al 2006).…”

Section: Introductionmentioning

confidence: 99%

High Serum HDGF Levels Are Predictive of Bone Metastasis and Unfavorable Prognosis in Non-Small Cell Lung Cancer

Zhang

Liu

Chen

et al. 2017

Tohoku J. Exp. Med.

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Hepatoma-derived growth factor (HDGF) is a heparin-binding protein possessing mitogenic activity and could be secreted from necrotic cells passively or actively, thereby functioning as a damage-associated molecular pattern (DAMP). The high expression of HDGF in non-small cell lung cancer (NSCLC) tissues is associated with unfavorable prognosis. However, the clinical significance of serum HDGF has not been elucidated in NSCLC yet. In the present study, we compared the serum levels of HDGF in 235 patients with NSCLC (141 adenocarcinoma and 94 squamous cell carcinoma cases) with those in 40 healthy subjects. Moreover, we explored the correlation between serum HDGF levels and clinicopathologic factors or the overall survival rates. We thus found that the serum HDGF levels were significantly higher in NSCLC patients than those in healthy subjects (P < 0.001). Moreover, there was no significant difference in the serum HDGF levels between adenocarcinoma and squamous cell carcinoma. Importantly, the higher serum levels of HDGF were significantly associated with bone metastasis and with lower overall survival rates. Thus, serum HDGF was identified as an independent prognostic factor indicating poor prognosis of NSCLC. Using A549 human lung adenocarcinoma cell line, we demonstrated that an autophagy inhibitor, chloroquine, could inhibit the HDGF secretion, while quercetin, an autophagy inducer derived from a traditional Chinese drug, could facilitate HDGF secretion. In conclusion, high serum levels of HDGF were significantly correlated to bone metastasis and poorer prognosis of NSCLC. We suggest that anti-HDGF therapy is potential to protect NSCLC patients with advanced stages from bone metastasis.

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Hepatoma‐derived growth factor promotes growth and metastasis of hepatocellular carcinoma cells

Yang

Zhang

Wang

et al. 2016

Cell Biochemistry & Function

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We aimed to elucidate the effects of hepatoma-derived growth factor (HDGF) on growth and metastasis of hepatocellular carcinoma (HCC) cells. Tissue microarrays with 236 HCC specimens and 18 extrahepatic metastases were utilized to detect the HDGF expression by immunohistochemistry. Meanwhile, HDGF expressions in HCC cell lines with different metastatic potentials were examined using immunofluorescence staining, real-time PCR and western blotting. After HDGF silencing, the growth and metastatic potentials of HCC cells were evaluated by soft agar assay, invasion assay, together with tumorigenicity assay in nude mice. The gelatin zymography was performed by detecting MMP-2 and MMP-9 levels. Additionally, western blotting was conducted to determine the levels of total and phosphorylated ERK1/2, JNK, p38 and Akt. The results showed that HDGF was overexpressed in HCC metastasis tumour, and the expression increased with the differentiation degree of tumours (Grade I 44.0%, Grade II 48.4% and Grade III 65.6%). Consistently, HDGF levels were positively associated with the metastatic capability of HCC cells (MHCC97L < MHCC97H < HCCLM3). The growth and metastasis were suppressed by HDGF-siRNA. Gelatinolytic activities were enhanced in the three metastatic HCC cell lines, but had no significant difference among them. The tumourigenicity and metastatic capability of HCCLM3 cells in nude mice were inhibited after silencing HDGF. Meanwhile, HDGF-siRNA specifically suppressed the total and phosphorylated protein levels of ERK1/2, while not JNK, p38 and Akt. In conclusion, HDGF was overexpressed in HCC patients and cells, and HDGF might be closely correlated with HCC metastasis via regulating ERK signalling pathway. Copyright © 2016 John Wiley & Sons, Ltd.

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Partial purification and characterization of human hepatoma-derived growth factor

Cited by 109 publications

References 10 publications

Hepatoma-derived Growth Factor

Hepatoma-derived Growth Factor

High Serum HDGF Levels Are Predictive of Bone Metastasis and Unfavorable Prognosis in Non-Small Cell Lung Cancer

Hepatoma‐derived growth factor promotes growth and metastasis of hepatocellular carcinoma cells

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