Expression and significance of Tie-1 and Tie-2 receptors, and angiopoietins-1, 2 and 4 in colorectal adenocarcinoma:Immunohistochemical analysis and correlation with clinicopathological factors

Nakayama, Toshiyuki

doi:10.3748/wjg.v11.i7.964

Cited by 44 publications

(35 citation statements)

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“…Angiopoietin family members usually regulate the differentiation or invasion of cancer cells through the activation of its receptor Tie-2 and downstream tyrosine kinase pathway (8,9,41). However, ANGPTL4 does not bind to Tie-2 but contains motifs structurally conserved in angiopoietins.…”

Section: Discussionmentioning

confidence: 99%

“…There is strong evidence that the angiopoietin family is involved in the regulation of tumour progression, cellular growth and differentiation (8)(9)(10). Angiopoietin-like 4 (ANGPTL4) is a member of the family of angiopoietins and is known as hepatic fibrinogen/angiopoietin-related protein (HEARP) (11), peroxisome proliferator-activated receptor-Á (PPARÁ) angiopoietin-related gene (PGAR) (12) or fastinginduced adipose factor (FIAF) (13).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

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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“…there is strong evidence that the angiopoietin family is involved in the regulation of tumour progression, cellular growth, and differentiation (4)(5)(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).…”

Section: Introductionmentioning

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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“…The coexpression of Ang-1, -2 and -4 and Tie-1 and -2 has been reported in tumor cells, suggesting the presence of an autocrine and/or a paracrine angiopoietin/Tie growth pathway in solid tumors [35][36][37][38] . Angiopoietins (Angs) also have been shown to play a role in the proliferation and/or differentiation of stromal tumors and normal mesenchymal cells [41,42] .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been found that Ang-1 and Ang-4 can activate Tie-1 [33] . Coexpression of angiopoietin and its receptor, either Tie-1 or Tie-2, has been reported in tumor cells, suggesting the presence of an autocrine and/or a paracrine angiopoietin/Tie growth pathway in solid tumors [34][35][36] . Further, the expression levels of angiopoietin and its receptors have been shown to correlate with progressive tumor growth and development of metastasis by many types of carcinomas [35][36][37][38] .…”

Section: Introductionmentioning

confidence: 99%

Expression of Angiopoietin-1, 2 and 4 and Tie-1 and 2 in gastrointestinal stromal tumor, leiomyoma and schwannoma

Nakayama

Inaba²,

Naito³

et al. 2007

WJG

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AIM:To investigate the role of angiopoietin (Ang) -1, -2 and -4 and its receptors, Tie-1 and -2, in the growth and differentiation of gastrointestinal stromal tumors (GISTs). METHODS:Thirty GISTs, seventeen leiomyomas and six schwannomas were examined by immunohistochemistry in this study. RESULTS:Ang-1, -2 and -4 proteins were expressed in the cytoplasm of tumor cells, and Tie-1 and -2 were expressed both in the cytoplasm and on the membrane of all tumors. Immunohistochemical staining revealed that 66.7% of GISTs (20 of 30), 76.5% of leiomyomas (13 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-1. 83.3% of GISTs (25 of 30), 82.4% of leiomyomas (14 of 17) and 100% of schwannomas (6 of 6) were positive for Ang-2. 36.7% of GISTs (11 of 30), 58.8% of leiomyomas (10 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-4. 60.0% of GISTs (18 of 30), 82.4% of leiomyomas and 100% of schwannomas (6 of 6) were positive for Tie-1. 10.0% of GISTs (3 of 30), 94.1% of leiomyomas (16 of 17) and 33.3% of schwannomas (2 of 6) were positive for Tie-2. Tie-2 expression was statistically different between GISTs and leiomyomas (P < 0.001). However, there was no correlation between expression of angiopoietin pathway components and clinical risk categories. CONCLUSION:Our results suggest that the angiopoietin pathway plays an important role in the differentiation of GISTs, leiomyomas and schwannomas.

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Expression and significance of Tie-1 and Tie-2 receptors, and angiopoietins-1, 2 and 4 in colorectal adenocarcinoma:Immunohistochemical analysis and correlation with clinicopathological factors

Abstract: These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human colorectal adenocarcinoma.

Cited by 44 publications

References 36 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

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

Expression of Angiopoietin-1, 2 and 4 and Tie-1 and 2 in gastrointestinal stromal tumor, leiomyoma and schwannoma

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