Connective Tissue Growth Factor Immunohistochemical Expression Is Associated With Gallbladder Cancer Progression

Context.— Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.— To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis. Design.— Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ2 test or Fisher exact probability test with a significance level of P < .05. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test. Results.— Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04). Conclusions.— Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.

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Connective tissue growth factor (CTGF) and cancer progression

Journal of Biomedical Science ◽

10.1007/s11373-008-9264-9 ◽

2008 ◽

Vol 15 (6) ◽

pp. 675-685 ◽

Cited By ~ 89

Author(s):

Chia-Yu Chu ◽

Cheng-Chi Chang ◽

Ekambaranellore Prakash ◽

Min-Liang Kuo

Keyword(s):

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Cancer Progression ◽

Tissue Growth

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Paraquat increases connective tissue growth factor expression and impairs lung fibroblast proliferation and viscoelasticity

Human & Experimental Toxicology ◽

10.1177/0960327114524239 ◽

2014 ◽

Vol 33 (12) ◽

pp. 1232-1240 ◽

Cited By ~ 4

Author(s):

N Zhang ◽

Y-P Xie ◽

L Pang ◽

X-X Zang ◽

J Wang ◽

...

Keyword(s):

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Molecular Mechanisms ◽

Tissue Growth ◽

Lung Fibroblasts ◽

Proliferation Index ◽

Enzyme Linked Immunosorbent Assay ◽

Dependent Manner ◽

Paraquat Poisoning

This in vitro study was designed to investigate the molecular mechanisms of paraquat-induced damage using cultured human fetal lung fibroblasts (MRC-5 cells), in order to promote the development of improved therapies for paraquat poisoning. Paraquat’s effects on proliferation were examined by flow cytometry, on viscoelasticity by the micropipette aspiration technique, and on connective tissue growth factor (CTGF) expression by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Paraquat was found to significantly reduce the proliferation index of MRC-5 cells in a concentration-dependent manner ( p < 0.05) and to significantly impair the viscoelastic properties in a time-independent manner ( p < 0.05). Exposure to paraquat led to a significant and time-dependent increase in CTGF expression ( p < 0.05) and induced changes in the morphology and biomechanical characteristics of the MRC-5 cells. These findings not only provide novel insights into the mechanisms of paraquat-induced lung fibrosis but may represent useful targets of improved molecular-based therapies for paraquat poisoning.

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Uptake and intracellular transport of the connective tissue growth factor: a potential mode of action

Biochemical Journal ◽

10.1042/bj3590089 ◽

2001 ◽

Vol 359 (1) ◽

pp. 89-97 ◽

Cited By ~ 25

Author(s):

Nadia Abdel WAHAB ◽

Heike BRINKMAN ◽

Roger M. MASON

Keyword(s):

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Intracellular Transport ◽

Molecular Mechanisms ◽

Mesangial Cells ◽

Tissue Growth ◽

Transport Pathway ◽

Potential Mode ◽

Fibrotic Disorders

Connective tissue growth factor (CTGF) is a secreted cysteine-rich protein now considered as an important effector molecule in both physiological and pathological processes. An increasing amount of evidence indicates that CTGF plays a key role in the pathogenesis of different fibrotic disorders including diabetic nephropathy. However, the molecular mechanisms by which CTGF exerts its effects are not known. Here we provide the first evidence for the existence of an intracellular transport pathway for the growth factor in human mesangial cells. Our results demonstrate that CTGF is internalized from the cell surface in endosomes and accumulates in a juxtanuclear organelle from which the growth factor is then translocated into the cytosol. In the cytosol CTGF is phosphorylated by protein kinase C and PMA treatment can enhance this phosphorylation. Phosphorylated CTGF may have an important role in the cytosol, but it is also translocated into the nucleus where it may directly affect transcription.

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