Inflammatory Mechanisms Contributing to Pancreatic Cancer Development

Farrow, Buckminster; Sugiyama, Yuko; Chen, Andy; Uffort, Ekong E.; Nealon, William H.; Evers, B. Mark

doi:10.1097/01.sla.0000128681.76786.07

Cited by 152 publications

(121 citation statements)

References 42 publications

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“…In fact, there is convincing evidence that cancer and inflammation share common signaling pathways. More specifically, pancreatic adenocarcinoma and chronic pancreatitis express a substantial proportion of proteins in common (22,25,26), placing patients that suffer from chronic pancreatitis at risk to develop pancreatic cancer (27). Indeed, mononuclear cells as mediators of nonspecific immune responses are recruited to pancreatic cancer and result in an angiogenic phenotype of cancer cells (21).…”

Section: Discussionmentioning

confidence: 99%

“…Little is known about the regulation of EFEMP1 expression in cancer. Because the microarray analyses had revealed an up-regulation of several mediators of inflammation pathways in L3.6pl cells and inflammatory cells have been reported to be involved in the development and progression of pancreatic cancer (21,22), we became interested in whether there was a link between IFN-a as a potent inflammatory stimulus and EFEMP1 expression in tumor cells. Interestingly, IFN-a provoked a >4-fold increase of EFEMP1 expression, as shown by quantitative RT-PCR (Fig.…”

Section: Differential Expression Of Efemp1 In Fg and L36pl Cells In mentioning

confidence: 99%

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EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

Seeliger¹,

Čamaj²,

Ischenko³

et al. 2009

Molecular Cancer Research

100

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The progression of pancreatic cancer is dependent on local tumor growth, angiogenesis, and metastasis. EFEMP1, a recently discovered member of the fibulin family, was characterized with regard to these key elements of pancreatic cancer progression. Differential gene expression was assessed by mRNA microarray hybridization in FG human pancreatic adenocarcinoma cells and L3.6pl cells, a highly metastatic variant of FG. In vivo orthotopic tumor growth of EFEMP1-transfected FG cells was examined in nude mice. To assess the angiogenic properties of EFEMP1, vascular endothelial growth factor (VEGF) production of tumor cells, endothelial cell proliferation and migration, and tumor microvessel density were analyzed in response to EFEMP1. Further, tumor cell apoptosis, cell cycle progression, and resistance to cytotoxic agents were quantitated by propidium iodide staining and flow cytometry. In microarray hybridization, EFEMP1 was shown to be significantly up-regulated in L3.6pl cells compared with FG cells. Concordantly, EFEMP1 transfection of FG cells stimulated orthotopic and metastatic tumor growth in vivo. EFEMP1 expression resulted in a stimulation of VEGF production by tumor cells and an increased number of CD31-positive microvessels. Endothelial cell proliferation and migration were not altered by EFEMP1, indicating an indirect angiogenic effect. Further, EFEMP1 expression decreased apoptosis and promoted cell cycle progression in response to serum starvation or exposure to gemcitabine, 5-fluorouracil, and irinotecan. EFEMP1 has protumorigenic effects on pancreatic cancer in vivo and in vitro mediated by VEGF-driven angiogenesis and antiapoptotic mechanisms. Hence, EFEMP1 is a promising candidate for assessing prognosis and individualizing therapy in a clinical tumor setting. (Mol Cancer Res 2009;7(2):189-98)

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Section: Discussionmentioning

confidence: 99%

Section: Differential Expression Of Efemp1 In Fg and L36pl Cells In mentioning

confidence: 99%

EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

Seeliger¹,

Čamaj²,

Ischenko³

et al. 2009

Molecular Cancer Research

100

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“…1a). This inflammatory and not neoplastic lesion is histologically characterized by a strong desmoplastic reaction, similar to PDAC, 27 while PDAC xenografts are a purified source of adenocarcinoma cells in vivo. To assess differential expression, a linear regression analysis was performed on logarithmic intensity values as a function of the sample class.…”

Section: A-enolase Is Overexpressed At Both Mrna and Protein Levelsmentioning

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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“…IL-8 is another inflammatory cytokine upregulated in both cancer and chronic inflammatory diseases of the pancreas. 24 It is linked to pancreatic cancer tumorigenesis primarily through its regulation of angiogenesis and metastasis. 25 The increase of IL-6 and IL-8 levels in pancreatic cancer cells by Tβ4 may cause increased cell proliferation and metastasis in pancreatic cancer, and therefore, enhance the pancreatic cancer pathogenesis and progression.…”

Section: Discussionmentioning

confidence: 99%

Thymosin beta 4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation

Zhang¹,

Feurino²,

Zhai³

et al. 2008

Cancer Biology & Therapy

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This manuscript has been published online, prior to printing.Once the issue is complete and page numbers have been assigned, the citation will change accordingly.Background: Thymosin beta 4 (Tβ4) has been shown to be associated with tumor metastasis and angiogenesis; however, its role in pancreatic cancer has not been understood. In the current study, we examined the expression of Tβ4 in pancreatic cancer cells, and determined the effect of exogenous Tβ4 on cytokine secretion, and signal transduction in human pancreatic cancer cells.Results Conclusions: Tβ4 might be involved in stimulating human pancreatic cancer progression by promoting proinflammatory cytokine environment and activating JNK signaling pathway. Targeting Tβ4 and related molecules may be a novel therapeutic strategy for pancreatic cancer.

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Inflammatory Mechanisms Contributing to Pancreatic Cancer Development

Cited by 152 publications

References 42 publications

EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

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

Thymosin beta 4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation

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