Expression of vascular endothelial growth factors A and C in human pancreatic cancer

Rui-feng, Tang; Wang, Shuxia; Li, Peng; Wang, Shunxiang; Zhang, Meng; Li, Zhifeng; Zhang, Zhiming; Yan, Xuemin; Zhang, Fengrui

doi:10.3748/wjg.v12.i2.280

Cited by 52 publications

(51 citation statements)

References 29 publications

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“…Taken together with the observation that EFEMP1 overexpression stimulates VEGF production in vivo, our findings are concordant with reports of the up-regulation of VEGF in pancreatic cancer (34)(35)(36). In contrast to our data that support a role of EFEMP1 in tumor progression in pancreatic adenocarcinoma, EFEMP1 expression was found down-regulated in lung cancer (37) and up-regulated in only 10% of different solid cancer entities (18).…”

Section: Discussioncontrasting

confidence: 53%

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: Discussioncontrasting

confidence: 53%

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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“…HIF helps to mediate responses to hypoxia (22). VEGF family members are commonly overexpressed in human pancreatic cancer and contribute to tumor growth and metastasis (23). We recently demonstrated that the metastatic potential of a human pancreatic cancer cell line HMET as compared with its nonmetastatic derivative LMET that was associated with increased expression of proangiogenic molecules, in particular, VEGF.…”

Section: Discussionmentioning

confidence: 98%

Hypoxia-Independent Gene Expression Mediated by SOX9 Promotes Aggressive Pancreatic Tumor Biology

Čamaj

Jäckel

Krebs

et al. 2014

Molecular Cancer Research

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Pancreatic cancer aggressiveness is characterized by its high capacity for local invasion, ability to promote angiogenesis, and potential to metastasize. Hypoxia is known to represent a crucial step in the development of aggressive malignant features of many human cancers. However, micrometastatic tumors are not typically subjected to hypoxic events during early stages of dissemination; therefore, it is unclear how these tumors are able to maintain their aggressive phenotype. Thus, the identification of regulators of hypoxia-related genes in aggressive/ metastatic tumors represents a fundamental step for the design of future therapies to treat pancreatic cancer. To this end, transcriptomic profiles were compared between the nonmetastatic pancreatic cancer cell line FG (LMET) and its angiogenic/metastatic derivate L3.6pl (HMET) under normoxic or hypoxic conditions. Cluster analysis revealed a number of transcripts that were induced by hypoxia in nonmetastatic cancer cells. Strikingly, this cluster was determined to be constitutively activated under normoxia in the metastatic cancer cells and could not be further induced by hypoxia. A subset of these transcripts were regulated by the transcription factor SOX9 in the aggressivemetastatic cells, but driven by hypoxia-inducible factor-1a (HIF-1a) in the parental nonmetastatic cell line. Moreover, these transcripts were enriched in cancer-related networks including: WNT, CXCR4, retinoic acid, and (FAK) focal adhesion kinase, gene PTK2 signaling pathways. In functional assays, inhibition of SOX9 expression in HMET cells led to increased apoptosis and reduced migration in vitro and a significant reduction in primary tumor growth, angiogenesis, and metastasis following orthotopic tumor cell injection. At the molecular level, the control of SOX9 expression was associated with changes in the methylation status of the SOX9 promoter. Finally, SOX9 upregulation was verified in a series of tumor specimens of patients with pancreatic carcinoma.

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“…Immunohistochemical analysis of 50 pancreatic cancer tissue samples revealed the presence of VEGF-A immunoreactivity in 50% of the cancer tissue samples. The presence of VEGF-A in these cells was associated with larger tumor size and enhanced local spread but it was not associated with decreased patient survival [82]. VEGF-A significantly increased the motility of pancreas cancer cells playing an important role in inducing invasion and migration of pancreatic cancer cells [83].…”

Section: Pancreatic Cancermentioning

confidence: 92%

“…Moreover, in human pancreatic cancer and nude mice model, the expression of VEGF-C on lymphatic metastasis was higher than in primary tumor [89]. The presence of VEGF-C in the cancer cells was associated with increased lymph node metastasis, but it was not associated with decreased patient survival [86,82].…”

Section: Pancreatic Cancermentioning

confidence: 99%

VEGF expression in pancreatic cancer and other malignancies: a review of the literature

Costache

Ioana

Iordache

et al. 2015

Romanian Journal of Internal Medicine

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Angiogenesis is a crucial event for tumor growth and it is regulated predominantly by several different growth factors. Vascular endothelial growth factor protein family (VEGF) and its receptors are probably the most important tissue factors responsible for angioblast differentiation and tube formation. VEGF protein family currently comprises several members: VEGF (or VEGF-A), VEGF-B, VEGF-C and VEGF-D, VEGF-F, placental growth factor (PlGF), and their receptors VEGFR-1, VEGFR-2 and VEGFR-3. VEGF is a key angiogenic growth factor and its level of expression is a critical marker for detection of the angiogenic diseases. The potent role of VEGF in tumor angiogenesis has been widely described in the past decade, being expressed in most types of nondigestive and digestive cancers. VEGF family members play an important role in the development of pancreatic cancer (especially VEGF-A, VEGF-C, VEGF-D, VEGFR-1 and VEGFR-2). VEGF-A is the most specific and prominent angiogenic factor among all family members and VEGFR-2 is the most important receptor in evaluating the angiogenesis in pancreatic cancer. Thus, VEGF overexpression may be considered as a diagnostic marker and as a poor prognostic factor of the disease.

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Expression of vascular endothelial growth factors A and C in human pancreatic cancer

Abstract: VEGF-A and VEGF-C are commonly overexpressed in human pancreatic cancer and may contribute to tumor growth and lymph node metastasis. There is no relationship between the expression of VEGF-A and VEGF-C in pancreatic cancer.

Cited by 52 publications

References 29 publications

EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

Hypoxia-Independent Gene Expression Mediated by SOX9 Promotes Aggressive Pancreatic Tumor Biology

VEGF expression in pancreatic cancer and other malignancies: a review of the literature

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