High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma

Seo, Yousuke; Baba, Hideo; Fukuda, Toshiro; Tomita, Masaki; Sugimachi, Keizō

doi:10.1002/(sici)1097-0142(20000515)88:10<2239::aid-cncr6>3.0.co;2-v

Cited by 384 publications

(224 citation statements)

References 29 publications

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“…In fact, significant downregulations of these mRNA expression levels were demonstrated in the retrovirally infected thyroid cell lines expressing the antisense HMGA2 (Vallone et al, 1997). Considering that the overexpression of the AP-1 (Tessari et al, 1999;Meggiato et al, 2003), VEGF (Seo et al, 2000), MMP-1 (Ito et al, 1999), and MMP-3 (Bramhall et al, 1996) has been demonstrated in human pancreatic cancer, together with our results, the interactions among these molecules may play an important role in pancreatic neoplastic transformation in vivo, Further studies, including the determination of expression levels of these molecules in tissue samples, have yet to be carried out to further clarify this issue. Conversely, the HMGA2 gene has recently been shown not to be necessary for the malignant transformation of thyroid cells in vivo (Scala et al, 2001).…”

Section: Discussionsupporting

confidence: 66%

An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue

et al. 2003

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The altered form of the high-mobility group A2 (HMGA2) gene is somehow related to the generation of human benign and malignant tumours of mesenchymal origin. However, only a few data on the expression of HMGA2 in malignant tumour originating from epithelial tissue are available. In this study, we examined the HMGA2 expression level in pancreatic carcinoma, and investigated whether alterations in the HMGA2 expression level are associated with a malignant phenotype in pancreatic tissue. High-mobility group A2 mRNA and protein expression was determined in eight surgically resected specimens of non-neoplastic tissue (six specimens of normal pancreatic tissue and two of chronic pancreatitis tissue) and 27 pancreatic carcinomas by highly sensitive reverse transcriptase -polymerase chain reaction (RT -PCR) techniques and immunohistochemical staining, respectively. Reverse transcriptase -polymerase chain reaction analysis revealed the expression of the HMGA2 gene in non-neoplastic pancreatic tissue, although its expression level was significantly lower than that in carcinoma. Immunohistochemical analysis indicated that the presence of the HMGA2 gene in non-neoplastic pancreatic tissue observed in RT -PCR reflects its abundant expression in islet cells, together with its focal expression in duct epithelial cells. Intense and multifocal or diffuse HMGA2 immunoreactivity was noted in all the pancreatic carcinoma examined. A strong correlation between HMGA2 overexpression and the diagnosis of carcinoma was statistically verified. Based on these findings, we propose that an increased expression level of the HMGA2 protein is closely associated with the malignant phenotype in the pancreatic exocrine system, and accordingly, HMGA2 could serve as a potential diagnostic molecular marker for distinguishing pancreatic malignant cells from non-neoplastic pancreatic exocrine cells.

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Section: Discussionsupporting

confidence: 66%

An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue

et al. 2003

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“…27 In patients with such neoplasia, VEGFA expression in the tumor and high serum concentration are significantly correlated to a decreased median survival time 37,38 and to metastasis progression, especially to the liver. 28 The correlation between VEGFA expression and the survival remains significant even after a surgery putatively considered as curative. 39 These results are consistent with the discovery that microvessel density and vascular proliferation index were significantly associated with larger tumor size and lymph node metastasis.…”

Section: Discussionmentioning

confidence: 99%

Myoferlin plays a key role in VEGFA secretion and impacts tumor‐associated angiogenesis in human pancreas cancer

Fahmy

Gonzalez

Arafa

et al. 2015

Intl Journal of Cancer

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Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin-silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density.

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“…Compared with normal pancreas and chronic pancreatitis, VEGF and its receptors were overexpressed in pancreatic cancer [73]. Seo Y et al demonstrated that 93% of ductal pancreatic adenocarcinomas were positive for VEGF protein [74]. A recent study shows a positive expression rate of VEGF 77% in pancreatic cancer tissues and 15% in adjacent normal pancreatic tissues [75].…”

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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High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma

Cited by 384 publications

References 29 publications

An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue

An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue

Myoferlin plays a key role in VEGFA secretion and impacts tumor‐associated angiogenesis in human pancreas cancer

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

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