Overexpression of alpha enolase in hepatitis?C virus-related hepatocellular carcinoma: Association with tumor progression as determined by proteomic analysis

Takashima, Motonari; Kuramitsu, Yasuhiro; Yokoyama, Yuichiro; Iizuka, Norio; Fujimoto, Masanori; Nishisaka, Takashi; Okita, Kiwamu; Oka, M.; Nakamura, Kazuyuki

doi:10.1002/pmic.200401022

Cited by 133 publications

(104 citation statements)

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“…[29][30][31] In addition, aenolase overexpression has been clinically associated with tumor status for lung and hepatocellular carcinoma. 32,33 a-Enolase induces an antibody response in almost two-third of PDAC patients, but not in healthy donors, non-PDAC tumor patients and chronic pancreatic patients. 18 PDAC patients did not display signs of autoimmunity, though the presence of anti-a-enolase antibodies has been described in patients with autoimmune disorders.…”

Section: Discussionmentioning

confidence: 99%

An integrated humoral and cellular response is elicited in pancreatic cancer by α‐enolase, a novel pancreatic ductal adenocarcinoma‐associated antigen

Cappello¹,

Tomaino²,

Chiarle³

et al. 2009

Intl Journal of Cancer

107

125

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Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5-year survival rate. a-Enolase is a glycolytic enzyme that also acts as a surface plasminogen receptor. We find that it is overexpressed in PDAC and present on the cell surface of PDAC cell lines. The clinical correlation of its expression with tumor status has been reported for lung and hepatocellular carcinoma. We have previously demonstrated that sera from PDAC patients contain IgG autoantibodies to a-enolase. The present work was intended to assess the ability of a-enolase to induce antigen-specific T cell responses. We show that a-enolase-pulsed dendritic cells (DC) specifically stimulate healthy autologous T cells to proliferate, secrete IFN-c and lyse PDAC cells but not normal cells. In vivo, a-enolase-specific T cells inhibited the growth of PDAC cells in immunodeficient mice. In 8 out of 12 PDAC patients with circulating IgG to a-enolase, the existence of a-enolase-specific T cells was also demonstrated. Taken as a whole, these results indicate that a-enolase elicits a PDAC-specific, integrated humoral and cellular response. It is thus a promising and clinically relevant molecular target candidate for immunotherapeutic approaches as new adjuvants to conventional treatments in pancreatic cancer. ' 2009 UICC

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Section: Discussionmentioning

confidence: 99%

An integrated humoral and cellular response is elicited in pancreatic cancer by α‐enolase, a novel pancreatic ductal adenocarcinoma‐associated antigen

Cappello¹,

Tomaino²,

Chiarle³

et al. 2009

Intl Journal of Cancer

107

125

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“…We found that MBP-1 may regulate tumor progression in gastric cancer through the MBP-1-COX-2 signaling axis. In addition to gastric cancer, MBP-1 was shown to participate in tumorigenesis of several tumors (Ray et al, 1995;Chang et al, 2003;Ejeskar et al, 2005;Ghosh et al, 2005a;Ghosh et al, 2005b;Takashima et al, 2005;Ghosh et al, 2006a;Ghosh et al, 2006b). Interestingly, COX-2 overexpression is observed in a variety of malignancies (Sano et al, 1995;Ristimäki et al, 1997;Hida et al, 1998;Zimmermann et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…MBP-1 and ␣-enolase are involved in tumorigenesis (Ray et al, 1995;Chang et al, 2003;Ejeskar et al, 2005;Ghosh et al, 2005a;Ghosh et al, 2005b;Takashima et al, 2005;Ghosh et al, 2006a;Ghosh et al, 2006b) and metastasis (Ray et al, 1995;Chang et al, 2003;Demir et al, 2005). It was proven that MBP-1 has the potential of a candidate for gene therapy against tumor growth (Chang et al, 2003;Ghosh et al, 2005b;Ghosh et al, 2006b).…”

Section: Discussionmentioning

confidence: 99%

“…Mounting evidence indicates that both MBP-1 and ␣-enolase are involved in tumorigenesis of breast carcinoma (Ray et al, 1995), nonsmall cell lung cancer (Chang et al, 2003;Ghosh et al, 2006b), hepatitis C virus-related hepatocellular carcinoma (Takashima et al, 2005), prostate tumor (Ghosh et al, 2005a;Ghosh et al, 2005b;Ghosh et al, 2006a), and neuroblastoma (Ejeskar et al, 2005). It was also suggested that MBP-1 expression reduces the invasive ability of breast cancer (Ray et al, 1995), and ␣-enolase may participate in control of EMT (Demir et al, 2005) and metastasis (Chang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

Hsu

Hsieh

et al. 2009

MBoC

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INTRODUCTIONGastric cancer is one of the most frequent neoplasms and leading causes of cancer-related mortality worldwide (Terry et al., 2002;Executive Yuan, 2006). At present, curative surgery of its primary tumor and control of lymph node metastasis are still the mainstay of treatment for gastric cancer without distant metastasis . However, gastric cancer with distant metastasis remains incurable now. More than 95% of malignancies of the stomach are adenocarcinomas (Smith et al., 2006). The risk factors of human gastric cancer include diet, Helicobacter pylori infection, and accumulation of specific genetic alterations (Gonzalez et al., 2002;Ushijima and Sasako, 2004;Zheng et al., 2004). To date, the regulatory mechanism of aggressiveness in gastric cancer has not yet been clearly characterized. Therefore, it is essential to gain further insights into the physiology of gastric cancer and its accumulated genetic alterations.The inducible cyclooxygenase, COX-2, catalyzes the ratelimiting step in conversion of arachidonate into prostaglandin E 2 (PGE 2 ). It was shown that COX-2 expression is upregulated in gastric cancer (Ristimäki et al., 1997;Uefuji et al., 1998;Yamamoto et al., 1999;Lim et al., 2000). COX-2 expression is also correlated with depth of invasion, lymphatic vessel invasion, lymph node metastasis, and poor prognosis of human gastric carcinoma (Murata et al., 1999;Ohno et al., 2001;Shi et al., 2003;Chen et al., 2006). Epithelial-mesenchymal transition (EMT) plays a key role in development and tumorigenesis (for a review, see Thiery and Sleeman, 2006). In gastric cancer cells with fibroblastoid morphological changes, EMT signaling was suggested to promote motility and invasiveness through decreasing cell-cell adhesion (Katoh, 2005). Recently, COX-2 expression was found to enhance EMT stimulated by TGF-␤ through a PGE 2 -dependent manner in breast cancer (Neil et al., 2008). In this scenario, the induction of COX-2 expression in gastric cancer could further induce EMT to promote metastasis.The c-Myc promoter binding protein 1 (MBP-1), a negative regulator of c-myc expression, is ubiquitously expressed in normal human tissues (Ray et al., 1994 groove of the major c-Myc promoter, the P2 promoter (Chaudhary and Miller, 1995). The 37-kDa MBP-1 is produced by alternative translation initiation from ␣-enolase gene but without enzyme activity of enolase (Feo et al., 2000;Subramanian and Miller, 2000). So far, several MBP-1-associating proteins were identified, including histone deacetylase HDAC1 (Ghosh et al., 1999), MIP2A/sedlin (Ghosh et al., 2001), MEK5␣ (Ghosh et al., 2005a), NS1-BP (Perconti et al., 2007), and Notch1 receptor intracellular domain (Hsu et al., 2008). The downstream target genes of MBP-1 remain unclear exclusive of c-myc. It was reported that MBP-1 could regulate target genes at least through p53-p21 pathway (Ghosh et al., 2008). Mounting evidence indicates that both MBP-1 and ␣-enolase are involved in tumorigenesis of breast carcinoma (Ray et al., 1995), nonsmall cell lung cancer (Chan...

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“…To date, clinical tissue samples have been the most extensively studied samples in HCC proteomic studies and most studies compared protein expression profiles between tumor tissue and adjacent non-tumor tissue Lim et al, 2002;Takashima et al, 2003Takashima et al, , 2005Yokoyama et al, 2004;Zeindl-Eberhart et al, 2004;Li et al, 2005). One study compared the protein profiles among HBV þ , HCV þ and HBVÀ/ HCVÀ HCC tumor tissues using 2D-PAGE-MS and found that among the 60 differentially expressed proteins when comparing tumor and non-tumor tissues, 46 proteins were specific to the underlying viral etiology (Kim et al, 2003).…”

Section: Tumor Tissuesmentioning

confidence: 99%