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843 SULF1 and SULF2 Correlated Genes in Hepatocellular Carcinoma (HCC) as Revealed by Genome-Wide Gene Expression Microarray Analysis
patients who did not feel involved in the process. A desire for shared decision-making and active involvement in care was expressed by 92% of patients. Conclusions: Surveillance rates for HCC at a tertiary care center are high at 78%. Most patients with cirrhosis express a strong desire to be actively involved in decisions regarding HCC surveillance and their care. Patient involvement is significantly correlated with higher surveillance rates and should be encouraged.
and Huh7 cells and xenograft-tumor growth in nude mice. METHODS: The HCC cell lines, HepG2 and Huh7 were used for these experiments. Adiponectin dose and time studies were conducted in the presence of leptin to determine cell viability by XTT-reduction and cell proliferation by BrdU incorporation. Metastatic properties, including the effect of adiponectin on leptin induced cell migration, were determined, by Electric Cell-substrate Impedance Sensing (ECIS) and scratch assay. The effect of adiponectin on leptin signaling was examined by immunoblot assay for phosphorylated STAT3 and Akt. We also elucidated the molecules involved in adiponectin signaling by immunoblot assay for LKB1-AMPK-TSC2-mTOR axis. HCC xenografts were produced in nude mice by injecting HepG2 cells. Nude mice with tumors were treated with recombinant leptin and/or adenoviral-adiponectin. RESULTS: Adiponectin treatment inhibited leptin-induced proliferation (XTT reduction and BrdU incorporation), and migration (ECIS assay) and scratch assay of HepG2 and Huh7 cells. Adiponectin treatment also inhibited leptin induced phosphorylation of STAT3 and Akt. Adiponectin decreased leptin induced phosphorylation of STAT3 by increasing the level of SOCS3. Adiponectin treatment alone significantly increased phosphorylation of AMPK via upstream regulator LKB1. Adiponectin induced AMPK inhibits mTOR via TSC2. Adiponectin treatment resulted in significant reduction of leptin induced tumor growth. CONCLUSIONS: Taken together, these data indicate that adiponectin has the potential to inhibit the malignant potential of leptin as adiponectin treatment leads to decreased cell proliferation and increased apoptosis of HCC cell lines and suppression of leptin induced tumor growth in nude mice.
842 Adenovirus-Mediated Hepatocyte Nuclear Factor 4a Prevents the Development of Hepatocellular Carcinoma in Rats Wei-Fen Xie, Bei-Fang Ning The majority of hepatocullular carcinoms (HCC) developed in cirrhotic liver. Unfortunately, effective strategies for HCC prevention in patients are still limited to date. It has been well demonstrated that hepatocyte nuclear factor 4α (HNF4α) plays a key role in hepatocyte differentiation and hepatic functions. Our previous study has indicated that up-regulation of HNF4α could induce the differentiation of both hepatoma cells and liver cancer stem cells into hepatocytes, implying that HNF4α might present as a novel therapeutic agent for HCC (Hepatology 2008). More recently, we also demonstrated that HNF4α plays a critical role in hepatic fibrogenesis, and forced expression of HNF4α remarkably ameliorated hepatic fibrosis in rats (Gut, 2009). In this study, rats were subjected to intraperitoneal injections of diethylinitrosamine for 10 weeks to establish HCC model. The rats were then divided into model group, GFP group and HNF4α group, which were infused with PBS, 5×109 pfu AdGFP (adenovirus carrying GFP gene) or AdHNF4α (adenovirus carrying HNF4α gene) via the tail vein every other week up to 10 weeks, respectively. Our results revealed the gradual reduction of HNF4α and epithelial-mesenchymal transition (EMT) during hepatocarcinogenesis, which could be significantly attenuated by adenovirus-mediated HNF4α delivery. More interestingly, the introduction of HNF4α remarkably alleviated hepatic fibrosis and entirely blocked HCC occurrence in rats. In contrast, all livers of model group and GFP control group exhibited neoplastic nodules at the 22nd week. Meanwhile, the expression of the potential markers for liver cancer stem/progenitor cells (CD133, CD90, EpCAM2 and OV6) were dramatically blocked by HNF4α introduction. Furthermore, forced expression of HNF4α not only decreased the activation of Wnt/β-catenin signaling, but also inhibited NF-ΚB signaling pathway, which were closely associated with EMT and hepatocarcinogenesis, suggesting the preventive effect of HNF4α on HCC development might be attributed to the suppression of β-catenin and NF-ΚB signaling. In conclusion, up-regulation of HNF4α may present as a promising strategy for HCC prevention in clinical practice, and the strategy using differentiation determining transcription factor for cancer prevention might be extended to other diseases.
The Smac Mimetic Jp1584 Reduces TRAIL-Induced Invasion and Metastasis of Cholangiocarcinoma Cells by Inhibiting NF-κB Activation Christian D. Fingas, Boris Blechacz, Rory Smoot, Maria Eugenia Guicciardi, Steven F. Bronk, Nathan W. Werneburg, Alphonse E. Sirica, Gregory J. Gores BACKGROUNDS AND AIMS: Cholangiocarcinoma is a devastating disease with limited therapeutic options. Paradoxically, these cancers express the death ligand TRAIL and its cognate receptors, which promote tumorigenicity in these apoptosis resistant cancers by enhancing NF-κB-mediated cell invasion and migration (Ishimura et al. American Journal of Physiology 290: G129-136, 2006). Smac mimetics are new cancer therapeutic agents, which enhance pro-apoptotic death receptor signaling by causing cellular degradation of inhibitors of apoptosis proteins (IAPs). Thus, our aims were to examine the effect of the Smac mimetic JP1584 in cholangiocarcinoma (CCA) cells In Vitro and In Vivo. METHODS: We employed the rat cholangiocarcinoma cell line BDEneu for these studies as they permit employment of an orthotopic, syngeneic, rodent model for In Vivo studies. RESULTS: Unexpectedly, TRAIL failed to induce apoptosis in BDEneu cells despite cellular loss of cIAP-1 and cIAP-2 during treatment with JP1584 (500 nM). As a positive control, JP1584 did enhance TRAIL-mediated apoptosis in a hepatocellular carcinoma cell line, Huh-7 cells. Because cIAP-1 and cIAP-2 also promote NF-κB activation by death receptors, we next examined the effect of JP1584 on this signaling pathway. Treatment of the cells with JP1584 did inhibit TRAIL-mediated phosphorylation of the p65 subunit of NF-κB and its nuclear translocation. This inhibition of TRAIL-induced NF-κB activation also reduced cell migration (cells/field; 74 ± 32 vs. 257 ± 95; p < 0.01) and invasion (RFU; 35 ± 2 vs. 55 ± 5; p < 0.05) in classic In Vitro assays. Next we confirmed that in a syngeneic rat, orthotopic CCA model (BDEneu cells; male Fischer 344 rats), BDEneu cells express TRAIL similar to human cancers as demonstrated by PCR, immunoblot and immunohistochemistry analysis. Administration of JP1584 did not effect intrahepatic tumor growth; however, the treated animals had minimal extrahepatic metastases as compared to untreated animals (11 % metastases in JP1584-treated animals vs. 67 % in untreated animals; p < 0.05). In CONCLUSION, the Smac mimetic JP1584 blocks TRAIL-induced migration/invasion of cholangiocarcinoma cells In Vitro and demonstrates anti-metastatic single-agent activity in an orthotopic syngeneic rodent model of cholangiocarcinoma. This effect is likely mediated by inhibition of TRAILinduced NF κB activation.
843 SULF1 and SULF2 Correlated Genes in Hepatocellular Carcinoma (HCC) as Revealed by Genome-Wide Gene Expression Microarray Analysis Ju Dong Yang, Zhifu Sun, Ju-Seog Lee, Snorri Thorgeirsson, Lewis R. Roberts Background/Aims: Limited information is available about the role of the heparin-degrading endosulfatases sulfatase 1 (SULF1) and sulfatase 2 (SULF2) in hepatocarcinogenesis. Functional studies performed thus far suggest that SULF1 functions as a tumor suppressor, in contrast, SULF2 has an oncogenic effect. The aim of this study is to characterize the role of SULF1 and SULF2 in human HCCs using high density oligonucleotide gene expression analysis. Methods: Microarray data available from a previous analysis of HCCs were used for this study. RNA from HCC and adjacent benign tissue from 139 individuals with HCC was analyzed at the National Cancer Institute using the Qiagen Human Array-Ready Oligo Set (version 2.0), which contains 70-mer probes for 21,329 genes. Partek and Metacore software were used to identify SULF1 and SULF2 correlated genes and to investigate the diseases and pathways associated with SULF1 and 2 correlated genes. The association between SULF2 expression and the hepatoblast/progenitor cell or hepatocyte HCC subtypes was also examined. Results: A total of 881 and 2,423 genes were correlated with SULF1 and SULF2 respectively while 559 genes were correlated with both SULF1 and 2 at a p value <0.001. SULF1 and 2 correlated genes were highly enriched in neoplasms including HCC. Cell adhesion, extracellular matrix remodeling, chemokines, cytoskeletal remodeling, TGF, and WNT were pathways highly enriched in SULF1 and SULF2 correlated genes. IQGAP1 (r= 0.68, p=4.1E-20), TGFB1 (r=0.62, p=2.5E-16) and Vimentin (r=0.57, p=2.0E-13) were genes that showed the strongest positive correlation with SULF2 while HNF4A (r=-0.63, p=3.3E-16) and IQGAP2 (r=-0.56, p=4.0E-13) had the strongest inverse correlation with SULF2 expression. 7 of the 10 HCCs (70%) with the highest ratio of tumor/benign SULF2 expression were of the hepatoblast subtype of HCC, compared to 15% hepatoblast subtype in the entire HCC samples set. Conclusion: A strong association was observed between SULF1 and 2 correlated genes and neoplasms including HCC. SULF1 and SULF2 have functional similarity in modulating cell adhesion, ECM remodeling, and WNT pathways. The positive and negative associations between SULF2 and the hepatoblast phenotype, TGFB, Wnt pathway, IQGAPs, and HNF4A are biologically plausible and remain to be fully investigated using laboratory experiments.
846 Putative Hepatic Cancer Stem Cells Have an Increased Antioxidant Capacity: Implications for the Development of a Metabolism-Based Strategy to Eradicate Liver Tumors Valentina Tesori, Anna C. Piscaglia, Laura Castellini, Marta Barba, Mariachiara Campanale, Luca Di Maurizio, Flaminia Purchiaroni, Annalisa Tortora, Tommaso Galeotti, Giovambattista Pani, Antonio Gasbarrini Background & Aim. Accumulating experimental evidence points to a hierarchical organization of tumors, at the apex of which a small subset of cancer stem cells (CSC) is located. Breast CSC have been reported to display a low content of reactive oxygen species (ROS) and an increased antioxidant capacity. This biochemical hallmark is likely due to a highly glycolytic metabolism and underlies tumor radioresistance. However, it is not known whether these features are specific to breast CSC or rather common to all CSC. In the present study antioxidant capacity, putative CSC content and response to the multikinase inhibitor Sorafenib (SFB) were investigated in LCSC liver cancer cell lines. Methods. We compared LCSC-2, endowed with an aggressive and drug-resistant phenotype, to LCSC-5, more differentiated and less tumorigenic. Intracellular ROS content was assessed by flow cytometry. Drug toxicity was evaluated through MTT assay. Results. Cytofluorimetric analysis of intracellular ROS content in LCSC-2 revealed the appearance, under serum deprivation, of a subpopulation of cells with a lower content of oxidant species; the percentage of these cells increased over time, indicating a relative resistance to growth factor withdrawal. Interestingly, this population was nearly absent in LCSC-5. Exposure to SFB increased intracellular ROS and led to a progressive enrichment of cells with low ROS. Since mitochondria are the main sources of ROS in normal and tumor cells, we reasoned that SFB may target these organelles, and thus spare the putative CSC, mainly dependent on glycolysis for their energy metabolism. To support our hypothesis, we tried SFB plus 2-deoxy-glucose (a glycolysis inhibitor): this combination dramatically increased SFB toxicity on LCSC-2 as well as on other cancer lines (human 293-T kidney carcinoma and murine B16F10 melanoma cells). Conclusions. Our preliminary results suggest the role of oxygen species in CSC self-renewal and chemoresistance in liver cancer lines and shed light on the mechanism of action of SFB.
844 Adiponectin Negatively Modulates the Pro-Cancerous Effects of Leptin on HEPG2 and Huh7 Cells and Xenograft-Tumor Growth in Nude Mice Arumugam Nagalingam, Ping Fu, Dipali Sharma, Frank A. Anania, Neeraj K. Saxena Obesity is an independent risk factor for hepatocellular carcinoma (HCC). Obese population maintains increased circulating levels of leptin as compared to decreased concentrations of serum adiponectin. Recently, we found that leptin-induced growth stimulation of HCC cells involves activation of Stat3, Akt and ERK. Leptin also promoted the invasion and migration of HCC cells. The PURPOSE of the present study was to demonstrate the potential mechanism whereby adiponectin negatively modulates the pro-cancerous effects of leptin on HepG2
S-797
AASLD Abstracts
AASLD Abstracts
845
and Huh7 cells and xenograft-tumor growth in nude mice. METHODS: The HCC cell lines, HepG2 and Huh7 were used for these experiments. Adiponectin dose and time studies were conducted in the presence of leptin to determine cell viability by XTT-reduction and cell proliferation by BrdU incorporation. Metastatic properties, including the effect of adiponectin on leptin induced cell migration, were determined, by Electric Cell-substrate Impedance Sensing (ECIS) and scratch assay. The effect of adiponectin on leptin signaling was examined by immunoblot assay for phosphorylated STAT3 and Akt. We also elucidated the molecules involved in adiponectin signaling by immunoblot assay for LKB1-AMPK-TSC2-mTOR axis. HCC xenografts were produced in nude mice by injecting HepG2 cells. Nude mice with tumors were treated with recombinant leptin and/or adenoviral-adiponectin. RESULTS: Adiponectin treatment inhibited leptin-induced proliferation (XTT reduction and BrdU incorporation), and migration (ECIS assay) and scratch assay of HepG2 and Huh7 cells. Adiponectin treatment also inhibited leptin induced phosphorylation of STAT3 and Akt. Adiponectin decreased leptin induced phosphorylation of STAT3 by increasing the level of SOCS3. Adiponectin treatment alone significantly increased phosphorylation of AMPK via upstream regulator LKB1. Adiponectin induced AMPK inhibits mTOR via TSC2. Adiponectin treatment resulted in significant reduction of leptin induced tumor growth. CONCLUSIONS: Taken together, these data indicate that adiponectin has the potential to inhibit the malignant potential of leptin as adiponectin treatment leads to decreased cell proliferation and increased apoptosis of HCC cell lines and suppression of leptin induced tumor growth in nude mice.
842 Adenovirus-Mediated Hepatocyte Nuclear Factor 4a Prevents the Development of Hepatocellular Carcinoma in Rats Wei-Fen Xie, Bei-Fang Ning The majority of hepatocullular carcinoms (HCC) developed in cirrhotic liver. Unfortunately, effective strategies for HCC prevention in patients are still limited to date. It has been well demonstrated that hepatocyte nuclear factor 4α (HNF4α) plays a key role in hepatocyte differentiation and hepatic functions. Our previous study has indicated that up-regulation of HNF4α could induce the differentiation of both hepatoma cells and liver cancer stem cells into hepatocytes, implying that HNF4α might present as a novel therapeutic agent for HCC (Hepatology 2008). More recently, we also demonstrated that HNF4α plays a critical role in hepatic fibrogenesis, and forced expression of HNF4α remarkably ameliorated hepatic fibrosis in rats (Gut, 2009). In this study, rats were subjected to intraperitoneal injections of diethylinitrosamine for 10 weeks to establish HCC model. The rats were then divided into model group, GFP group and HNF4α group, which were infused with PBS, 5×109 pfu AdGFP (adenovirus carrying GFP gene) or AdHNF4α (adenovirus carrying HNF4α gene) via the tail vein every other week up to 10 weeks, respectively. Our results revealed the gradual reduction of HNF4α and epithelial-mesenchymal transition (EMT) during hepatocarcinogenesis, which could be significantly attenuated by adenovirus-mediated HNF4α delivery. More interestingly, the introduction of HNF4α remarkably alleviated hepatic fibrosis and entirely blocked HCC occurrence in rats. In contrast, all livers of model group and GFP control group exhibited neoplastic nodules at the 22nd week. Meanwhile, the expression of the potential markers for liver cancer stem/progenitor cells (CD133, CD90, EpCAM2 and OV6) were dramatically blocked by HNF4α introduction. Furthermore, forced expression of HNF4α not only decreased the activation of Wnt/β-catenin signaling, but also inhibited NF-ΚB signaling pathway, which were closely associated with EMT and hepatocarcinogenesis, suggesting the preventive effect of HNF4α on HCC development might be attributed to the suppression of β-catenin and NF-ΚB signaling. In conclusion, up-regulation of HNF4α may present as a promising strategy for HCC prevention in clinical practice, and the strategy using differentiation determining transcription factor for cancer prevention might be extended to other diseases.
The Smac Mimetic Jp1584 Reduces TRAIL-Induced Invasion and Metastasis of Cholangiocarcinoma Cells by Inhibiting NF-κB Activation Christian D. Fingas, Boris Blechacz, Rory Smoot, Maria Eugenia Guicciardi, Steven F. Bronk, Nathan W. Werneburg, Alphonse E. Sirica, Gregory J. Gores BACKGROUNDS AND AIMS: Cholangiocarcinoma is a devastating disease with limited therapeutic options. Paradoxically, these cancers express the death ligand TRAIL and its cognate receptors, which promote tumorigenicity in these apoptosis resistant cancers by enhancing NF-κB-mediated cell invasion and migration (Ishimura et al. American Journal of Physiology 290: G129-136, 2006). Smac mimetics are new cancer therapeutic agents, which enhance pro-apoptotic death receptor signaling by causing cellular degradation of inhibitors of apoptosis proteins (IAPs). Thus, our aims were to examine the effect of the Smac mimetic JP1584 in cholangiocarcinoma (CCA) cells In Vitro and In Vivo. METHODS: We employed the rat cholangiocarcinoma cell line BDEneu for these studies as they permit employment of an orthotopic, syngeneic, rodent model for In Vivo studies. RESULTS: Unexpectedly, TRAIL failed to induce apoptosis in BDEneu cells despite cellular loss of cIAP-1 and cIAP-2 during treatment with JP1584 (500 nM). As a positive control, JP1584 did enhance TRAIL-mediated apoptosis in a hepatocellular carcinoma cell line, Huh-7 cells. Because cIAP-1 and cIAP-2 also promote NF-κB activation by death receptors, we next examined the effect of JP1584 on this signaling pathway. Treatment of the cells with JP1584 did inhibit TRAIL-mediated phosphorylation of the p65 subunit of NF-κB and its nuclear translocation. This inhibition of TRAIL-induced NF-κB activation also reduced cell migration (cells/field; 74 ± 32 vs. 257 ± 95; p < 0.01) and invasion (RFU; 35 ± 2 vs. 55 ± 5; p < 0.05) in classic In Vitro assays. Next we confirmed that in a syngeneic rat, orthotopic CCA model (BDEneu cells; male Fischer 344 rats), BDEneu cells express TRAIL similar to human cancers as demonstrated by PCR, immunoblot and immunohistochemistry analysis. Administration of JP1584 did not effect intrahepatic tumor growth; however, the treated animals had minimal extrahepatic metastases as compared to untreated animals (11 % metastases in JP1584-treated animals vs. 67 % in untreated animals; p < 0.05). In CONCLUSION, the Smac mimetic JP1584 blocks TRAIL-induced migration/invasion of cholangiocarcinoma cells In Vitro and demonstrates anti-metastatic single-agent activity in an orthotopic syngeneic rodent model of cholangiocarcinoma. This effect is likely mediated by inhibition of TRAILinduced NF κB activation.
843 SULF1 and SULF2 Correlated Genes in Hepatocellular Carcinoma (HCC) as Revealed by Genome-Wide Gene Expression Microarray Analysis Ju Dong Yang, Zhifu Sun, Ju-Seog Lee, Snorri Thorgeirsson, Lewis R. Roberts Background/Aims: Limited information is available about the role of the heparin-degrading endosulfatases sulfatase 1 (SULF1) and sulfatase 2 (SULF2) in hepatocarcinogenesis. Functional studies performed thus far suggest that SULF1 functions as a tumor suppressor, in contrast, SULF2 has an oncogenic effect. The aim of this study is to characterize the role of SULF1 and SULF2 in human HCCs using high density oligonucleotide gene expression analysis. Methods: Microarray data available from a previous analysis of HCCs were used for this study. RNA from HCC and adjacent benign tissue from 139 individuals with HCC was analyzed at the National Cancer Institute using the Qiagen Human Array-Ready Oligo Set (version 2.0), which contains 70-mer probes for 21,329 genes. Partek and Metacore software were used to identify SULF1 and SULF2 correlated genes and to investigate the diseases and pathways associated with SULF1 and 2 correlated genes. The association between SULF2 expression and the hepatoblast/progenitor cell or hepatocyte HCC subtypes was also examined. Results: A total of 881 and 2,423 genes were correlated with SULF1 and SULF2 respectively while 559 genes were correlated with both SULF1 and 2 at a p value <0.001. SULF1 and 2 correlated genes were highly enriched in neoplasms including HCC. Cell adhesion, extracellular matrix remodeling, chemokines, cytoskeletal remodeling, TGF, and WNT were pathways highly enriched in SULF1 and SULF2 correlated genes. IQGAP1 (r= 0.68, p=4.1E-20), TGFB1 (r=0.62, p=2.5E-16) and Vimentin (r=0.57, p=2.0E-13) were genes that showed the strongest positive correlation with SULF2 while HNF4A (r=-0.63, p=3.3E-16) and IQGAP2 (r=-0.56, p=4.0E-13) had the strongest inverse correlation with SULF2 expression. 7 of the 10 HCCs (70%) with the highest ratio of tumor/benign SULF2 expression were of the hepatoblast subtype of HCC, compared to 15% hepatoblast subtype in the entire HCC samples set. Conclusion: A strong association was observed between SULF1 and 2 correlated genes and neoplasms including HCC. SULF1 and SULF2 have functional similarity in modulating cell adhesion, ECM remodeling, and WNT pathways. The positive and negative associations between SULF2 and the hepatoblast phenotype, TGFB, Wnt pathway, IQGAPs, and HNF4A are biologically plausible and remain to be fully investigated using laboratory experiments.
846 Putative Hepatic Cancer Stem Cells Have an Increased Antioxidant Capacity: Implications for the Development of a Metabolism-Based Strategy to Eradicate Liver Tumors Valentina Tesori, Anna C. Piscaglia, Laura Castellini, Marta Barba, Mariachiara Campanale, Luca Di Maurizio, Flaminia Purchiaroni, Annalisa Tortora, Tommaso Galeotti, Giovambattista Pani, Antonio Gasbarrini Background & Aim. Accumulating experimental evidence points to a hierarchical organization of tumors, at the apex of which a small subset of cancer stem cells (CSC) is located. Breast CSC have been reported to display a low content of reactive oxygen species (ROS) and an increased antioxidant capacity. This biochemical hallmark is likely due to a highly glycolytic metabolism and underlies tumor radioresistance. However, it is not known whether these features are specific to breast CSC or rather common to all CSC. In the present study antioxidant capacity, putative CSC content and response to the multikinase inhibitor Sorafenib (SFB) were investigated in LCSC liver cancer cell lines. Methods. We compared LCSC-2, endowed with an aggressive and drug-resistant phenotype, to LCSC-5, more differentiated and less tumorigenic. Intracellular ROS content was assessed by flow cytometry. Drug toxicity was evaluated through MTT assay. Results. Cytofluorimetric analysis of intracellular ROS content in LCSC-2 revealed the appearance, under serum deprivation, of a subpopulation of cells with a lower content of oxidant species; the percentage of these cells increased over time, indicating a relative resistance to growth factor withdrawal. Interestingly, this population was nearly absent in LCSC-5. Exposure to SFB increased intracellular ROS and led to a progressive enrichment of cells with low ROS. Since mitochondria are the main sources of ROS in normal and tumor cells, we reasoned that SFB may target these organelles, and thus spare the putative CSC, mainly dependent on glycolysis for their energy metabolism. To support our hypothesis, we tried SFB plus 2-deoxy-glucose (a glycolysis inhibitor): this combination dramatically increased SFB toxicity on LCSC-2 as well as on other cancer lines (human 293-T kidney carcinoma and murine B16F10 melanoma cells). Conclusions. Our preliminary results suggest the role of oxygen species in CSC self-renewal and chemoresistance in liver cancer lines and shed light on the mechanism of action of SFB.
844 Adiponectin Negatively Modulates the Pro-Cancerous Effects of Leptin on HEPG2 and Huh7 Cells and Xenograft-Tumor Growth in Nude Mice Arumugam Nagalingam, Ping Fu, Dipali Sharma, Frank A. Anania, Neeraj K. Saxena Obesity is an independent risk factor for hepatocellular carcinoma (HCC). Obese population maintains increased circulating levels of leptin as compared to decreased concentrations of serum adiponectin. Recently, we found that leptin-induced growth stimulation of HCC cells involves activation of Stat3, Akt and ERK. Leptin also promoted the invasion and migration of HCC cells. The PURPOSE of the present study was to demonstrate the potential mechanism whereby adiponectin negatively modulates the pro-cancerous effects of leptin on HepG2
S-797
AASLD Abstracts
AASLD Abstracts
845