The Relationship Between Microvessel Density, the Expression of Vascular Endothelial Growth Factor (VEGF), and the Extension of Nasopharyngeal Carcinoma

Huang, Guangwu; Sunagawa, Makoto; Li, Jieen; Shimada, Seiji; Zeng, Gang; Tokeshi, Yoshihiro; Kosugi, Tadayoshi

doi:10.1097/00005537-200012000-00017

Cited by 104 publications

(68 citation statements)

References 23 publications

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“…[35][36][37] Furthermore, VEGF expression was found to be markedly increased and correlated with microvessel density in nasopharyngeal carcinoma patients. 30 Similarly, we herein found that TNFAIP2 is a downstream target of TNFa that acts as a potential angiogenic factor, as shown by the association of its expression with microvessel density in vivo.…”

Section: Discussionsupporting

confidence: 75%

“…Finally, we tested for a potential interaction between TNFAIP2 and VEGF, an important secreted angiogenesis-initiating factor that has also been correlated with microvessel density in nasopharyngeal carcinoma patients. 30 As the protein sequence of TNFAIP2 (amino acids 91-651) is highly similar to that of SEC6 (based on a publicly available website http://www.sanger.ac.uk/), an exocyst complex component involved in exocytosis 31 and secretion, 32 we examined whether TNFAIP2 affected the secretion of VEGF by HK1 cells. As shown in Figure 3d, our results revealed that VEGF secretion by HK1 cells was not affected by TNFAIP2 knockdown.…”

Section: Promotion Of Cell Migration and Invasion By Tnfaip2mentioning

confidence: 99%

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A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma

Chen

et al. 2011

Modern Pathology

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Tumor necrosis factor alpha (TNFa) is an inflammatory cytokine that is present in the microenvironment of many tumors and is known to promote tumor progression. To examine how TNFa modulates the progression and metastasis of nasopharyngeal carcinoma, we used Affymetrix chips to identify TNFa-inducible genes that are dysregulated in this tumor. Elevated expression of TNFAIP2, which encodes TNFa-inducible protein 2 and not previously known to be associated with cancer, was found and confirmed by quantitative RT-PCR of TNFAIP2 expression in nasopharyngeal carcinoma and adjacent normal tissues. Immunohistochemical analysis showed that the TNFAIP2 protein was highly expressed in tumor cells. Analysis of 95 nasopharyngeal carcinoma biopsy specimens revealed that high TNFAIP2 expression was significantly correlated with highlevel intratumoral microvessel density (P ¼ 0.005) and low distant metastasis-free survival (P ¼ 0.001). A multivariate analysis further confirmed that TNFAIP2 was an independent prognostic factor for nasopharyngeal carcinoma (P ¼ 0.002). In vitro, TNFa treatment of nasopharyngeal carcinoma HK1 cells was found to induce TNFAIP2 expression, and siRNA-based knockdown of TNFAIP2 dramatically reduced the migration and invasion of nasopharyngeal carcinoma HK1 cells. These results collectively suggest for the first time that TNFAIP2 is a cell migration-promoting protein and its expression predicts distant metastasis. Our data suggest that TNFAIP2 may serve as an independent prognostic indicator for nasopharyngeal carcinoma.

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Section: Discussionsupporting

confidence: 75%

Section: Promotion Of Cell Migration and Invasion By Tnfaip2mentioning

confidence: 99%

A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma

Chen

et al. 2011

Modern Pathology

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“…VEGF is a key angiogenic stimulator, and its expression can directly induce angiogenesis. It is a prognostic factor and is highly expressed in metastatic cancers, including NPC (22,23). IL-8 is proangiogenic (24) and contributes to a poor prognosis in primary NPC (25).…”

Section: Discussionmentioning

confidence: 99%

Cysteine-rich intestinal protein 2 ( CRIP2 ) acts as a repressor of NF-κB–mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis

Cheung¹,

Ko²,

Lung³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Chromosome 14 was transferred into tumorigenic nasopharyngeal carcinoma and esophageal carcinoma cell lines by a microcellmediated chromosome transfer approach. Functional complementation of defects present in the cancer cells suppressed tumor formation. A candidate tumor-suppressor gene, cysteine-rich intestinal protein 2 (CRIP2), located in the hot spot for chromosomal loss at 14q32.3, was identified as an important candidate gene capable of functionally suppressing tumor formation. Previous studies have shown that CRIP2 is associated with development. To date, no report has provided functional evidence supporting a role for CRIP2 in tumor development. The present study provides unequivocal evidence that CRIP2 can functionally suppress tumorigenesis. CRIP2 is significantly down-regulated in nasopharyngeal carcinoma cell lines and tumors. CRIP2 reexpression functionally suppresses in vivo tumorigenesis and angiogenesis; these effects are induced by its transcription-repressor capability. It interacts with the NF-κB/p65 to inhibit its DNA-binding ability to the promoter regions of the major proangiogenesis cytokines critical for tumor progression, including IL6, IL8, and VEGF. In conclusion, we provide compelling evidence that CRIP2 acts as a transcription repressor of the NF-κB-mediated proangiogenic cytokine expression and thus functionally inhibits tumor formation and angiogenesis.transcription regulator | antiangiogenesis

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“…Tumor MVD is a significant and independent prognostic indicator for relapse-free and overall survival of cancer patients [152]. Similarly, elevated tumor or serum levels of the pro-angiogenic factors VEGF-A, interleukin (IL) and FGF-2 as well as a low ratio between the angiogenesis inhibitor thrombospondin-2 and VEGF-A are associated with an increased incidence of metastasis in cancer patients [153][154][155]. Xenograft animal models confirm the correlation of tumoral overexpression of angiogenic growth factors, increased MVD of primary and secondary tumors and metastasis formation [156][157][158].…”

Section: Tumor Angiogenesismentioning

confidence: 99%

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Kopfstein

Christofori

2006

Cell. Mol. Life Sci.

209

160

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Abstract. The fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent formation of metastases. During tumor progression, some of the primary tumor cells as well as the tumor microenvironment undergo characteristic molecular changes, which are essential for the metastatic dissemination of tumor cells. In this review, we will discuss recent insights into pro-metastatic events occurring in tumor cells themselves and in the tumor stroma. Tumor cell-intrinsic alterations include the loss of cell polarity and alterations in cell-cell and cell-matrix Cell. Mol. Life Sci. 63 (2006) 449-468 1420-682X/06/040449-20 DOI 10.1007/s00018-005-5296-8 © Birkhäuser Verlag, Basel, 2006 adhesion as well as deregulated receptor kinase signaling, which together support detachment, migration and invasion of tumor cells. On the other hand, the tumor stroma, including endothelial cells, fibroblasts and cells of the immune system, is engaged in an active molecular crosstalk within the tumor microenvironment. Subsequent activation of blood vessel and lymph vessel angiogenesis together with inflammatory and immune-suppressive responses further promotes cancer cell migration and invasion, as well as initiation of the metastatic process.

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The Relationship Between Microvessel Density, the Expression of Vascular Endothelial Growth Factor (VEGF), and the Extension of Nasopharyngeal Carcinoma

Abstract: The metastatic potency of NPC tissue and the prognosis of the patients with NPC can be estimated by measuring MVD and the expression of VEGF in NPC tissue. Drugs that have inhibitory actions on angiogenesis could be useful to prevent metastasis of NPC cells in the patients.

Cited by 104 publications

References 23 publications

A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma

A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma

Cysteine-rich intestinal protein 2 ( CRIP2 ) acts as a repressor of NF-κB–mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

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