Disease relevance of HDGF

• HDGF was more highly expressed in the lungs of idiopathic pulmonary fibrosis, chiefly in the epithelial cells, than in control nonfibrotic lungs [1].
• This suggests that HDGF may play a critical role in the development and progression of lung cancer [2].
• HDGF exhibits mitogenic activities for certain hepatoma cells, fibroblasts and vascular smooth muscle cells, and angiogenic activities through nuclear targeting [2].
• We investigated, immunohistochemically, the relationship between HDGF expression and clinicopathological variables, and the prognostic significance of HDGF in 102 patients with completely resected non-small-cell lung cancer (NSCLC: 70 adenocarcinomas and 32 squamous cell carcinomas) [2].
• In contrast, biopsies of melanoma showed strong expression of HDGF throughout the tumor, including cells located deeply within dermis [3].
• These findings suggest that HDGF could be a novel prognostic factor for pancreatic ductal carcinoma [4].

High impact information on HDGF

• We also detected native HDGF in nuclei of cultured SMCs, of SMCs and endothelial cells from 19-day fetal (but not in the adult) rat aorta, of SMCs proximal to abdominal aortic constriction in adult rats, and of SMCs in the neointima formed after endothelial denudation of the rat common carotid artery [5].
• Here, we demonstrate that HDGF mRNA is expressed in smooth muscle cells (SMCs), most prominently in proliferating SMCs, 8-24 hours after serum stimulation [5].
• Hepatoma-derived growth factor (HDGF) is the first member identified of a new family of secreted heparin-binding growth factors highly expressed in the fetal aorta [5].
• Rat aortic SMCs transfected with a hemagglutinin-epitope-tagged rat HDGF cDNA contain HA-HDGF in their nuclei during S-phase [5].
• We report that the protein kinase C activator beta-phorbol 12,13-dibutyrate (PDBu) suppresses bovine capillary endothelial (BCE) cell proliferation (K50 = 6 +/- 4 nM) and DNA synthesis in response to human hepatoma-derived growth factor, an angiogenic endothelial mitogen [6].

Chemical compound and disease context of HDGF

• Hepatoma-derived growth factor was also more strongly expressed in the tumors than in the adjacent fatty liver of fatty liver Shionogi (FLS) mice, than in the cirrhotic liver of choline-deficient amino acid feeding rats, as shown by northern blotting and immunohistochemistry [7].
• Bioassay and Western blotting of fast protein liquid chromatography fractions of tissue extracts identified platelet-derived growth factor, heparin-binding epidermal growth factor, hepatoma-derived growth factor, and basic fibroblast growth factor in normal myometrium and fibroid tumors [8].

Biological context of HDGF

• According to double immunostaining for endothelial cells with a transforming growth factor-betaII receptor antibody and BrdU as a marker of cell proliferation, exogenous HDGF selectively stimulated endothelial cell BrdU uptake [9].
• Adenoviral overexpression of HDGF was mitogenic for human pulmonary microvascular endothelial cells in serum-free medium, stimulating a 1.75-fold increase in bromodeoxyuridine (BrdU) uptake and a twofold increase in cell migration [9].
• Because of these roles, HDGF is a potential target for drug design [10].
• Hepatoma-derived growth factor stimulates smooth muscle cell growth and is expressed in vascular development [5].
• Transfection with HDGF-specific small interfering RNA (siRNA) resulted in down-regulation of HDGF expression in four NSCLC cell lines [11].

Anatomical context of HDGF

• With the chick chorioallantoic membrane (CAM), a biologic assay for angiogenesis, exogenous recombinant HDGF significantly stimulated blood vessel formation and a dose-dependent reorganization of cells within the CAM into a more compact, linear alignment reminiscent of tube formation [9].
• Hepatoma-derived growth factor (HDGF) was previously identified as a developmentally regulated cardiovascular and renal gene that is mitogenic for vascular smooth muscle and aortic endothelial cells [9].
• In vivo intratracheal instillation of recombinant HDGF induced the proliferation of bronchial and alveolar epithelial cells without causing marked interstitial inflammation [1].
• It is suggested that HDGF was secreted or released from these foci and stimulated hepatocyte proliferation in a paracrine manner in FLS mice, and stimulated the proliferation of hepatic tumor cells in an autocrine manner [7].
• Hepatoma Derived Growth Factor (HDGF) was originally identified as a secreted mitogen from the human hepatoma cell line Huh-7 [10].

Associations of HDGF with chemical compounds

• In contrast, expression in the PDT-resistant variants was downregulated for NNX3, human HepG2 3' region Mbol complementary DNA, glutamate dehydrogenase, hepatoma-derived growth factor and the mitochondrial genes coding for 16S ribosomal RNA (rRNA) and nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 4 [12].

Regulatory relationships of HDGF

• We conclude that HDGF is a highly expressed vascular endothelial cell protein in vivo and is a potent endothelial mitogen and regulator of endothelial cell migration by mechanisms distinct from VEGF [9].

Other interactions of HDGF

• The administration of anti-VEGF neutralizing antibody significantly suppressed, but did not block, the tumor growth of HDGF-overexpressing cells in nude mice [13].
• Hepatoma-derived growth factor (HDGF), unrelated to hepatocyte growth factor, is a heparin-binding protein originally purified from human hepatoma HuH-7 cells [2].
• HDGF is structurally related to basic fibroblast growth factor (FGF) [14].
• This study investigated the correlation of HDGF expression with differentiation and prognosis of hepatocellular carcinoma (HCC) [15].
• In particular, hepatoma-derived growth factor (HDGF) and nucleophosmin B23 were strongly correlated with melanoma [3].

Analytical, diagnostic and therapeutic context of HDGF

• According to immunohistochemistry, HDGF was highly expressed in endothelial cells of nonmuscularized, forming blood vessels of the fetal lung [9].
• By Western immunoblotting, HDGF was highly expressed by human pulmonary microvascular endothelial cells in vitro [9].
• We also confirmed the expression of HDGF protein and mRNA in the lungs of bleomycin-instilled mice, mainly in the bronchial and alveolar epithelial cells, by immunohistochemical analysis and in situ hybridization [1].
• METHODS: Expression of HDGF was analyzed using northern blotting and immunohistochemistry in the human and rodent models [7].
• Sequence analysis of tryptic fragments demonstrates that HDGF contains sequences that are homologous to both amino-terminal and carboxyl-terminal sequences of basic FGF [14].

References