High Clusterin Expression Correlates with a Poor Outcome in Stage II Colorectal Cancers

Kevans, David; Foley, J.R.; Tenniswood, Martin; Sheahan, Kieran; Hyland, John; O’Donoghue, Diarmuid; Mulcahy, Hugh; O'Sullivan, Jacintha

doi:10.1158/1055-9965.epi-08-0302

Cited by 35 publications

(27 citation statements)

References 41 publications

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“…The results of the present study support the association of clusterin expression with lymph node metastasis and perineural invasion, and thus with aggressive tumor behavior of pancreatic adenocarcinoma. These findings are consistent with those of other studies performed on gastrointestinal adenocarcinomas, in which cytoplasmic clusterin expression was found to be associated with lymph node metastasis and significantly shorter survival in advanced gastric cancer [27], and colorectal cancer [28,29]. The exact mechanism of clusterin overexpression in enhancing cancer metastasis is still unclear.…”

Section: Discussionsupporting

confidence: 92%

Clinical significance of clusterin expression in pancreatic adenocarcinoma

Jin¹,

Kim²,

Hur³

et al. 2012

World J Surg Onc

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BackgroundClusterin is known to be expressed in many human neoplasms, and is believed to participate in the regeneration, migration, and anti-apoptosis of tumor cells. However, few reports have addressed the relationship between the manifestation of clusterin and clinicopathologic parameters in pancreas cancer patients. In the present study, the authors investigated the expression of clusterin and its clinical significance in pancreatic adenocarcinoma.MethodsImmunohistochemical staining was performed for clusterin in tumor tissues obtained from patients who received pancreatic resection with radical intent, and the associations of clusterin expression with various clinicopathologic parameters were analyzed in addition to the relation between its expression and survival.ResultsImmunoreactivity for clusterin was observed in 17 of the 52 (33%) pancreatic adenocarcinomas examined. In addition, clusterin positivity was found to be associated with preoperative serum carcinoembryonic antigen level, perineural invasion, and, most strongly, lymph node metastasis. The survival analysis identified tumor differentiation and lymph node metastasis as the only significant prognostic factors.ConclusionAlthough not an independent prognostic factor, clusterin immunoreactivity can be used in conjunction with lymph node metastasis to predict survival in cases of pancreatic adenocarcinoma.

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Section: Discussionsupporting

confidence: 92%

Clinical significance of clusterin expression in pancreatic adenocarcinoma

Jin¹,

Kim²,

Hur³

et al. 2012

World J Surg Onc

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“…CLUSTERIN PROTECTS THE KIDNEY FROM INJURY expression is associated with progression of many types of cancers in patients (25,28,38,52), and antisense oligodeoxynucleotides targeting Clu expression in cancer cells increases cell death or decreases cell survival in the response to the treatment with chemotherapeutic drugs, growth factor withdrawal, and oxidative H 2 O 2 , respectively (16,17,32,56). To date, the mechanisms by which Clu acts differently in neural cells vs. cardiac and renal cells are not known.…”

Section: F575mentioning

confidence: 99%

Loss of clusterin expression worsens renal ischemia-reperfusion injury

Zhou

Guan

Kwan

et al. 2010

American Journal of Physiology-Renal Physiology

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Prevention of ischemia-reperfusion injury (IRI) is a challenge in clinical care of the patients with kidney transplants or acute kidney injury, and understanding of the intrinsic mechanisms of resistance to injury in the kidney will lead to a novel therapy. Clusterin, a secreted glycoprotein, is an antiapoptotic protein in cancer cells. Our study is to investigate the role of clusterin in renal IRI. Renal IRI in mice was induced by clamping renal vein and artery for 45 or 50 min at 32 degrees C. Apoptosis of renal tubular epithelial cells (TECs) was determined by FACS analysis. Clusterin expression was examined by Western blot or immunohistochemistry. Here, we showed that clusterin protein was induced in TECs following IRI, and more tubules expressed clusterin in the kidneys following ischemia at higher temperatures. In human proximal TEC HKC-8 cultures, clusterin was upregulated by removal of serum and growth factors in medium and was downregulated by TNF-alpha-IFN-gamma mixture. The levels of clusterin were positively correlated with cell survival in these conditions. Knockdown or knockout of clusterin expression enhanced the sensitivity of TECs to apoptosis. In experimental models of renal IRI, deficiency in clusterin expression worsened the injury, as indicated by a significant increase in renal tissue damage with higher levels of serum creatinine and blood urea nitrogen and by a poorer recovery from the injury in clusterin-deficient mice compared with wild-type mice. Our data indicate that the reduction of inducible expression of clusterin results in an increase in TEC apoptosis in the cultures and renders mice susceptibility to IRI, implying a protective role of clusterin in kidney injury.

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“…sCLU overexpression reaches a maximum at three to four days post-castration and coincides with the onset of massive cell death [3]. The sCLU level also rises in various malignant tumors, including gastric cancer [4], ovarian cancer [5], breast cancer [6], bladder cancer [7], colorectal cancer [8], hepatocellular carcinoma [9], prostate cancer [10] and laryngeal squamous cell carcinomas [11]. In these cancers, sCLU overexpression has been reported to be closely associated with cancer development and progression.…”

Section: Introductionmentioning

confidence: 99%

Clusterin silencing inhibits proliferation and reduces invasion in human laryngeal squamous carcinoma cells

Wang¹,

Cao

et al. 2014

World J Surg Onc

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BackgroundClusterin is, in its major form, a secreted heterodimeric disulfide-linked glycoprotein (sCLU), which plays important roles in cell survival and death. In laryngeal squamous cell carcinomas (LSCC), sCLU is up-regulated and its expression is related to the invasiveness of these tumors. The purpose of this study was to explore the inhibiting role of sCLU gene silence in the invasive ability and growth of Hep-2 human laryngeal squamous carcinoma cells (Hep-2) by transfection of short hairpin RNA expression plasmids against sCLU (sCLU-shRNA) (in vivo) or small interference RNA (sCLU-siRNA) (in vitro).MethodssCLU-siRNA and the control siRNA were transfected into Hep-2 cells using Lipofectamine 2000. RT-PCR and Western blot were used to detect the effect of siRNA transfection on sCLU mRNA and sCLU protein expression. The invasive activity of sCLU-siRNA-transfected Hep-2 cells was measured with the modified Boyden chamber assay and wound healing assay. The effects of sCLU-siRNA on cell proliferation were evaluated by MTT assay. Apoptosis was measured by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-staining methods. We next evaluated the effects of sCLU silencing by sCLU-shRNA transfection in vivo on tumor growth and metastatic properties to the lung. Terminal deoxytransferase-mediated dUTP nick end labeling (TUNEL) staining was used to observe the apoptosis in the xenografts.ResultsIt showed that siRNA-mediated down-regulation of sCLU expression in Hep-2 cells significantly inhibited cell proliferation and promoted apoptosis in vitro. Furthermore, siRNA-mediated down-regulation of sCLU expression decreases in vitro cell migration and invasion ability. In vivo, the average volume of tumors in the sCLU-shRNA transfected group was significantly lower than in the control group (P <0.01), and the significant apoptosis detected with TUNEL was indicated in the sCLU-shRNA transfected groups (P <0.05). Significantly, we found that sCLU-shRNA could exert marked inhibition of the lung metastasis of Hep-2 cells in nude mice in vivo.ConclusionssCLU gene silence can inhibit invasion and growth of LSCC. sCLU may provide a potential therapeutic target against human LSCC.

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High Clusterin Expression Correlates with a Poor Outcome in Stage II Colorectal Cancers

Cited by 35 publications

References 41 publications

Clinical significance of clusterin expression in pancreatic adenocarcinoma

Clinical significance of clusterin expression in pancreatic adenocarcinoma

Loss of clusterin expression worsens renal ischemia-reperfusion injury

Clusterin silencing inhibits proliferation and reduces invasion in human laryngeal squamous carcinoma cells

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