Angiopoietin-Related/Angiopoietin-Like Proteins Regulate Angiogenesis

Oike, Yuichi; Yasunaga, Kunio; Suda, Toshio

doi:10.1532/ijh97.04034

Cited by 133 publications

(131 citation statements)

References 48 publications

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“…ANGPTL4 is known as a gene with hypoxia-induced expression in endothelial cells. This protein is up-regulated by fasting and peroxisome proliferator-activated receptor agonists, associates with lipoproteins (12), and is involved in regulating glucose homeostasis, insulin sensitivity and lipid metabolism (12,(16)(17)(18). However, the role of ANGPTL4 is not clarified in cancer biology, although the role of ANGPTL4 has been well characterized in ischemic conditions and lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Expression of angiopoietin-like 4 in human gastric cancer: ANGPTL4 promotes venous invasion

Nakayama¹

2010

Oncol Rep

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Abstract. There is strong evidence that the angiopoietin family is involved in the regulation of tumour progression, cellular growth and differentiation. Recently, it has been reported that angiopoietin-like 4 (ANGPTL4) in cancer cell promotes the metastatic process by increasing vascular permeability. To elucidate ANGPTL4 expression and its association with clinicopathological factors and prognosis in human gastric adenocarcinomas, we examined 103 cases of surgicallyresected human gastric adenocarcinoma by immunohistochemistry. Among 103 cases of adenocarcinoma, 38 cases (36.9%) showed positive staining in the cytoplasm of the carcinoma cells for ANGPTL4. Histologically, papillary and mucinous adenocarcinomas showed relatively high expression of ANGPTL4 (60 and 60%, respectively). The expression of ANGPTL4 was correlated with the depth of tumour invasion (p<0.005), lymph node metastasis (p<0.001), venous invasion (p<0.00005) and TNM stage (p<0.001) in the total carcinoma. In univariate survival analysis, ANGPTL4 expression was not associated with the overall survival. RT-PCR or Western blot analysis showed the expression of mRNA or protein of ANGPTL4 in all four surgically-resected samples and all four cell lines of human gastric adenocarcinoma. ANGPTL4 expression was correlated with several clinicopathological factors, especially venous invasion. These findings suggest that the ANGPTL4 is one of the factors involved in the progression of human gastric cancer. IntroductionGastric cancer is one of the most common cancer types in the world today, in spite of the fact that its incidence has shown a gradual decline in many countries (1). The occurrence and progression of cancer are considered to be a series of genetic events affecting the structure and/or expression of a number of oncogenes, tumour suppressors and growth factors (2,3). The deep invasive carcinomas, such as gastric cancer, have higher rates of lymph duct and venous invasions and lymph node metastasis (4). However, the mechanisms of invasion and metastasis of gastric carcinoma are not fully understood.The molecular mechanisms in tumour progression, local invasion and the formation of tumour metastases represent a major challenge in cancer research. Metastasis of tumour cells is the primary cause of death in patients with cancer (5). To metastasize, tumour cells undergo a multistep progression through a series of sequential and selective events (6). The metastatic process consists of tumour cell detachment, local invasion, motility, angiogenesis, vessel invasion, survival in the circulation, adhesion to endothelial cells, extravasation and regrowth in different organs (7). In each step, causative molecules have been identified; these include cell-adhesion molecules, various growth factors, matrix degradation enzymes and motility factors, of which most of these can be regarded as prognostic factors (7).There is strong evidence that the angiopoietin family is involved in the regulation of tumour progression, cellular growth and differentiation (8-10). A...

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Section: Introductionmentioning

confidence: 99%

Expression of angiopoietin-like 4 in human gastric cancer: ANGPTL4 promotes venous invasion

Nakayama¹

2010

Oncol Rep

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“…Recently novel members of the angiopoietin subfamily, angiopoietin-related proteins (ARPs) or angiopoietinlike proteins (ANGPTLS) family, have been discovered. ARPs/ANGPTLS are characterized by a failure to bind Tie 2, despite having the characteristic domain of angiopoietins [12]. Angiopoietin-like 3 (ANGPTL3) consists of 460 amino acids in humans, and 455 amino Angptl3 gene is predominantly expressed in the liver [1].…”

Section: Introductionmentioning

confidence: 99%

Angptl3-null Mice Show Low Plasma Lipid Concentrations by Enhanced Lipoprotein Lipase Activity

et al. 2006

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“…Angptl4 induces a strong proangiogenic response, independently of vascular endothelial growth factor (11), and is known to undergo hypoxia-induced gene expression in endothelial cells. this protein is up-regulated by fasting and peroxisome proliferator-activated receptor agonists, associates with lipoproteins (8), and is involved in regulating glucose homeostasis, insulin sensitivity, and lipid metabolism through its ability to inhibit lipoprotein lipase (8,(12)(13)(14). However, the role of Angptl4 is little known in cancer biology, although the role of Angptl4 has been well characterized in ischemic conditions and lipid metabolism.…”

mentioning

confidence: 99%

Expression of angiopoietin-like 4 (ANGPTL4) in human colorectal cancer: ANGPTL4 promotes venous invasion and distant metastasis

Nakayama

Hirakawa²,

Shibata³

et al. 2011

Oncol Rep

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Abstract. there is strong evidence that the angiopoietin family is involved in the regulation of tumour progression. recently, it has been reported that angiopoietin-like 4 (Angptl4) expression in cancer cells promotes the metastatic process by increasing vascular permeability. the present study was conducted to examine Angptl4 expression and its association with clinicopathological factors and prognosis in human colorectal cancers. We examined 144 cases of surgically-resected human colorectal adenocarcinomas by immunohistochemistry, rt-pcr and Western blot analysis. Also, overall survival was investigated. Among 144 cases of adenocarcinoma, 95 cases (66.0%) showed positive staining in the cytoplasm of the carcinoma cells for Angptl4. Histologically, well, moderately, poorly differentiated adenocarcinoma or mucinous carcinoma showed 55.2, 79.3, 61.5 or 44.4% expression of Angptl4, respectively. the expression of Angptl4 was correlated with the depth of tumour invasion (p<0.0005), Vienna classification (category 3-5) (p<0.00005), venous invasion (p<0.0005) and Duke's classification (p<0.005). However, Angptl4 expression was not correlated with overall survival. However, all patients (100%) with distant metastasis showed immunopositivity for Angptl4. the mrnA and the protein expression of Angptl4 were shown in four resected samples and cultured cell lines by rt-pcr or Western blot analysis. These findings suggest that Angptl4 is one of the factors involved in the progression of human colorectal cancer, especially venous invasion and distant metastasis. Introductioncolorectal cancer is one of the most common cancer types in the world today (1). the occurrence and progression of cancer are considered to be a series of genetic events affecting the structure and/or expression of a number of oncogenes, tumour suppressors, and growth factors (2,3). the deep invasive carcinomas, such as colorectal cancer, have higher rates of lymph duct and venous invasions, and lymph node metastasis (3). However, the mechanisms of invasion and metastasis of colorectal cancer are not fully understood.there is strong evidence that the angiopoietin family is involved in the regulation of tumour progression, cellular growth, and differentiation (4-6). Angiopoietin-like 4 (Angptl4) is a member of the family of angiopoietins and is also known as hepatic fibrinogen/angiopoietin-related protein (HeArp) (7), peroxisome proliferator-activated receptor-γ (ppArγ) angiopoietin-related gene (pgAr) (8), or fasting-induced adipose factor (FIAF) (9). Angptl4 is a circulating plasma protein and is expressed in the liver, adipose tissue, placenta, as well as in ischemic tissue (8,9). similar to angiopoietins and other angiopoietin-like proteins, Angptl4 contains an amino-terminal coiled-coil domain and a carboxyl-terminal fibrinogen-like domain (10). Angptl4 induces a strong proangiogenic response, independently of vascular endothelial growth factor (11), and is known to undergo hypoxia-induced gene expression in endothelial cells. this protein is up-regu...

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Angiopoietin-Related/Angiopoietin-Like Proteins Regulate Angiogenesis

Cited by 133 publications

References 48 publications

Expression of angiopoietin-like 4 in human gastric cancer: ANGPTL4 promotes venous invasion

Expression of angiopoietin-like 4 in human gastric cancer: ANGPTL4 promotes venous invasion

Angptl3-null Mice Show Low Plasma Lipid Concentrations by Enhanced Lipoprotein Lipase Activity

Expression of angiopoietin-like 4 (ANGPTL4) in human colorectal cancer: ANGPTL4 promotes venous invasion and distant metastasis

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