ArticleWorld journal of gastroenterology2012
Connective tissue growth factor is overexpressed in human hepatocellular carcinoma and promotes cell invasion and growth.
Article in World journal of gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- CTGF (CCN2): a multifaceted mediator in breast cancer progression and therapeutic targeting.Cancer metastasis reviews · 2025Review
- BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation.BMC cancer · 2022Article
- RNA-seq data analysis of stimulated hepatocellular carcinoma cells treated with epigallocatechin gallate and fisetin reveals target genes and action mechanisms.Computational and structural biotechnology journal · 2020Article
- Three Dimensional Mixed-Cell Spheroids Mimic Stroma-Mediated Chemoresistance and Invasive Migration in hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2018Article
- Development of Normal and Cleft Palate: A Central Role for Connective Tissue Growth Factor (CTGF)/CCN2.Journal of developmental biology · 2018Review
- CCN3 is a therapeutic target relating enhanced stemness and coagulation in hepatocellular carcinoma.Scientific reports · 2017Article
- The pivotal role of CCN2 in mammalian palatogenesis.Journal of cell communication and signaling · 2017Article
- miR-133b Regulation of Connective Tissue Growth Factor: A Novel Mechanism in Liver Pathology.The American journal of pathology · 2016Article
- CCN: core regulatory proteins in the microenvironment that affect the metastasis of hepatocellular carcinoma?Oncotarget · 2016Review
- Members of the Cyr61/CTGF/NOV Protein Family: Emerging Players in Hepatic Progenitor Cell Activation and Intrahepatic Cholangiocarcinoma.Gastroenterology research and practice · 2016Article
- Evaluation of tumor metastasis-associated markers for molecular classification in patients with esophageal squamous cell carcinoma.International journal of clinical and experimental medicine · 2015Article
- Expression of connective tissue growth factor in male breast cancer: clinicopathologic correlations and prognostic value.PloS one · 2015Article
- CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d.Oncotarget · 2014Article
- Article
- Nonlinear quantitative radiation sensitivity prediction model based on NCI-60 cancer cell lines.TheScientificWorldJournal · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
aimTo determine the expression characteristics of connective tissue growth factor (CTGF/CCN2) in human hepatocellular carcinoma (HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression and metastasis in vitro.
methodsLiver samples from 36 patients (who underwent hepatic resection for the first HCC between 2006 and 2011) and 6 normal individuals were examined for transforming growth factor β1 (TGF-β1) or CCN2 mRNA by in situ hybridization. Computer image analysis was performed to measure integrated optimal density of CCN2 mRNA-positive cells in carcinoma foci and the surrounding stroma. Fibroblast-specific protein-1 (FSP-1) and E-cadherin were examined to evaluate the process of epithelial to mesenchymal transition, α-smooth muscle actin and FSP-1 were detected to identify hepatic stellate cells, and CD34 was measured to evaluate the extent of vascularization in liver tissues by immunohistochemical staining. CCN2 was assessed for its stimulation of HepG2 cell migration and invasion using commercial kits while flow cytometry was used to determine CCN2 effects on HepG2 cell-cycle.
resultsIn situ hybridization analysis showed that TGF-β1 mRNA was mainly detected in connective tissues and vasculature around carcinoma foci. In comparison to normal controls, CCN2 mRNA was enhanced 1.9-fold in carcinoma foci (12.36 ± 6.08 vs 6.42 ± 2.35) or 9.4-fold in the surrounding stroma (60.27 ± 28.71 vs 6.42 ± 2.35), with concomitant expression of CCN2 and TGF-β1 mRNA in those areas. Epithelial-mesenchymal transition phenotype related with CCN2 was detected in 12/36 (33.3%) of HCC liver samples at the edges between carcinoma foci and vasculature. Incubation of HepG2 cells with CCN2 (100 ng/mL) resulted in more of the cells transitioning into S phase (23.85 ± 2.35 vs 10.94 ± 0.23), and induced a significant migratory (4.0-fold) and invasive (5.7-fold) effect. TGF-β1-induced cell invasion was abrogated by a neutralizing CCN2 antibody showing that CCN2 is a downstream mediator of TGF-β1-induced hepatoma cell invasion.
conclusionThese data support a role for CCN2 in the growth and metastasis of HCC and highlight CCN2 as a potential novel therapeutic target.
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