CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients

Zhang, Qing; Chen, Xinguo; Zhou, Jun; Zhang, Li; Zhao, Qingchuan; Chen, Guangsheng; Xu, Jing; Feng, Qian; Chen, Zhi‐Nan

doi:10.4161/cbt.5.7.2754

Cited by 92 publications

(87 citation statements)

References 30 publications

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“…It was associated with tumor recurrence-free survival and could be used as a significant independent predictor of poor survival in HCC patients after tumor resection (17). For the HCC patients who received liver transplantation, CD147 was also found to be a significant predictor of tumor recurrence combined with the expression of CD34, a marker of microvessel density, and the expression of MMP-2 and MMP-9 in stromal compartment (18). The expression of tumor vascular endothelial growth factor (VEGF) was also positively correlated with that of CD147 (17).…”

Section: Introductionmentioning

confidence: 86%

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

Xu¹,

Xu²,

Zhang³

et al. 2007

Molecular Cancer Research

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144

134

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CD147 molecule is reported to be correlated with the malignancy of some cancers; however, it remains unclear whether it is involved in the progression of hepatocellular carcinoma (HCC). Here, we investigated the function of HAb18G/CD147, a member of CD147 family, and its antibodies, HAb18 and LICARTIN, in HCC invasion and metastasis. We observed that HAb18G/CD147 gene silence in HCC cells significantly decreased the secretion of matrix metalloproteinase (MMP) and the invasive potential of HCC cells (P < 0.001). MMP silence in HCC cells also significantly suppressed the invasion of the cells when cocultured with fibroblasts; however, its inhibitory effect was significantly weaker than that of both HAb18G/CD147 silence in HCC cells and that of MMP silence in fibroblasts (P < 0.001). Blocking the HAb18G/CD147 molecule on HCC cells with HAb18 monoclonal antibody resulted in a similar suppressive effect on MMP secretion and cell invasion, but with no significant effects on the cell growth. 131 I-labeled HAb18 F(ab ¶) 2 (LICARTIN), however, significantly inhibited the in vitro growth of HCC cells (P < 0.001). In an orthotopic model of HCC in nude mice, HAb18 and LICARTIN treatment effectively reduced the tumor growth and metastasis as well as the expression of three major factors in the HCC microenviroment (MMPs, vascular endothelial growth factor, and fibroblast surface protein) in the paracancer tissues. Overall, these results suggest that HAb18G/CD147 plays an important role in HCC invasion and metastasis mainly via modulating fibroblasts, as well as HCC cells themselves to disrupt the HCC microenviroment. LICARTIN can be used as a drug targeting to HAb18G/ CD147 in antimetastasis and recurrence therapy of HCC.

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Section: Introductionmentioning

confidence: 86%

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

Xu¹,

Xu²,

Zhang³

et al. 2007

Molecular Cancer Research

Self Cite

144

134

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“…Fluorescence resonance energy transfer analyses suggest that the minimal complex consists of a dimer of CD147 interacting with two MCT1 molecules . Aggressive tumors were found to express higher than usual levels of CD147, which corresponded with up-regulated levels of MCT1 (Froberg et al 2001;Nabeshima et al 2006;Zhang et al 2006); an event potentially necessary to meet the high glycolytic needs of transformed cells. Recently, expression of MCT4 was shown to control plasma membrane localization of CD147 in a metastatic breast cancer cell line (Gallagher et al 2007).…”

Section: Mctmentioning

confidence: 99%

“…Since MCT surface expression is linked to CD147 due to the requirement for interaction between the two proteins for successful cell surface expression (Kirk et al 2000), a coordinate upregulation of CD147 is observed on tumor cells. Indeed, screening of numerous clinical tumor specimens consistently reveals a link between the most aggressive tumors and the highest expression levels of CD147 Rosenthal et al 2003;Ishibashi et al 2004;Reimers et al 2004;Cheng et al 2006;Nabeshima et al 2006;Riethdorf et al 2006;Vigneswaran et al 2006;Zhang et al 2006;Zheng et al 2006). Increased expression of CD147 results in induction of increased MMP production by peritumoral fibrobasts resulting in degradation of the extracellular matrix and a favorable environment for tumor metastasis ( Figure 1B).…”

Section: Hypoxic Induction Of Mct and Cd147 Expression Promotes Tumormentioning

confidence: 99%

CD147 immunoglobulin superfamily receptor function and role in pathology

Iacono

Brown

Greene

et al. 2007

Experimental and Molecular Pathology

243

206

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The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer's disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is introduced.

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“…In total, there were four tissue OS studies (Chow et al, 1997;Jeng et al, 2004a;Deli et al, 2005;Sheen et al, 2005), six tissue DFS studies (Jeng et al, 2004a;Sheen et al, 2005;Guo et al, 2006;Wada et al, 2006;Zhang et al, 2006;Ho et al, 2007), seven serum OS studies (Poon et al, 2001(Poon et al, , 2004a(Poon et al, , b, 2007Chao et al, 2003;Kim et al, 2004;Jeng et al, 2004b;Treiber et al, 2006), and five serum DFS studies (Poon et al, 2001(Poon et al, , 2007Chao et al, 2003;Jeng et al, 2004b;Treiber et al, 2006). Pooled HRs were then calculated for all groups.…”

Section: Summary Estimates Of Primary Studiesmentioning

confidence: 99%

Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

et al. 2009

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Hepatocellular carcinoma (HCC) is a highly vascular tumour that expresses vascular endothelial growth factor (VEGF). Various studies have evaluated the prognostic value of VEGF levels in HCC. Its overall test performance remains unclear, however. The aim was to perform a systematic review and meta-analysis of prognostic cohort studies evaluating the use of VEGF as a predictor of survival in patients with treated HCC. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Newcastle–Ottawa Tool. Data were collected comparing disease-free and overall survival in patients with high VEGF levels as compared to those with low levels. Studies were pooled and summary hazard ratios were calculated. A total of 16 studies were included for meta-analysis (8 for tissue and 8 for serum). Methodological analysis indicated a trend for higher study quality with serum studies as compared to tissue-based investigations. Four distinct groups were pooled for analysis: tissue overall survival ( n =251), tissue disease-free survival ( n =413), serum overall survival ( n =579), and serum disease-free survival ( n =439). High tissue VEGF levels predicted poor overall (HR=2.15, 95% CI: 1.26–3.68) and disease-free (HR=1.69, 95% CI: 1.23–2.33) survival. Similarly, high serum VEGF levels predicted poor overall (HR=2.35, 95% CI: 1.80–3.07) and disease-free (HR=2.36, 95% CI 1.76–3.16) survival. A high degree of inter-study consistency was present in three of four groups analysed. Tissue and serum VEGF levels appear to have significant predictive ability for estimating overall survival in HCC and may be useful for defining prognosis in HCC.

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CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients

Abstract: The tumor biomarkers CD147 and MVD-CD34 are more feasible markers for rational selection of LT candidates with HCC. MMP-9 and MMP-2 expression in stromal compartment, combined with pTNM tumor grade, may be helpful in predicting poor prognosis in HCC patients after LT.

Cited by 92 publications

References 30 publications

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

CD147 immunoglobulin superfamily receptor function and role in pathology

Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

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