Epstein-Barr virus latent membrane protein 1 is not associated with vessel density nor with hypoxia inducible factor 1 alpha expression in nasopharyngeal carcinoma tissue

被引：22

作者：

Benders A.A. ^{[1
,2
]}

Tang W. ^{[1
]}

Middeldorp J.M. ^{[2
]}

Greijer A.E. ^{[2
]}

Thorne L.B. ^{[1
]}

Funkhouser W.K. ^{[1
]}

Rathmell W.K. ^{[3
]}

Gulley M.L. ^{[1
]}

机构：

[1] Department of Pathology and Laboratory Medicine, The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7525, 101 Manning Dr

[2] Department of Pathology, VU University Medical Center, Amsterdam

[3] Departments of Medicine and Genetics, The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC

来源：

Head and Neck Pathology | 2009年 / 3卷 / 4期

关键词：

Angiogenesis; HIF-1α; Immunohistochemistry; Nasopharyngeal carcinoma;

D O I：

10.1007/s12105-009-0148-8

中图分类号：

学科分类号：

摘要：

Hypoxia-inducible factor-1α (HIF-1α) and the neo-angiogenic factors induced as a result of hypoxia-inducible factor transcriptional activation may contribute to tumorigenesis by inducing vessel formation that in turn provides oxygen and nutrients promoting tumor expansion. In vitro studies of nasopharyngeal carcinoma (NPC), an aggressive malignancy that is nearly always infected by Epstein-Barr virus, show HIF-1α is upregulated by viral latent membrane protein 1 (LMP1). The current study used immunohistochemistry to examine the extent to which HIF-1α and LMP1 are co-expressed in naturally infected NPC tissues. Analytic procedures were optimized for sensitive localization of HIF-1α and LMP1 in fixed tissue sections using immunohistochemistry with sensitive fluorescent and signal amplification technologies. Vessel density was quantified by CD31 immunohistochemistry. LMP1 was expressed focally in all 18 NPCs examined, including 7/8 in situ lesions. There was no consistent co-localization with HIF-1α which was usually only weakly expressed in a subset of neoplastic cells. Neither LMP1 nor HIF-1α expression correlated with vessel density, and degree of vascularization varied widely among cases. Advanced immunohistochemical technologies reveal that LMP1 is expressed more commonly than previously reported in NPC. There is no consistent relationship between LMP1 and either HIF-1α expression or degree of microvasculature. The biologic basis for the wide variation in vessel density deserves further investigation. © Humana 2009.

引用

页码：276 / 282

页数：6

共 34 条

[1]

Delongchamps N.B., Peyromaure M., The role of vascular endothelial growth factor in kidney and prostate cancer, Can J Urol, 14, 5, pp. 3669-3677, (2007)

[2]

Sgadari C., Barillari G., Toschi E., Et al., HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma, Nat Med, 8, 3, pp. 225-232, (2002)

[3]

Gulley M.L., Tang W., Laboratory assays for Epstein-Barr virus-related disease, J Mol Diagn, 10, 4, pp. 279-292, (2008)

[4]

Raab-traub N., Flynn K., Pearson G., Et al., The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA, Int J Cancer, 39, 1, pp. 25-29, (1987)

[5]

Guang-wu H., Sunagawa M., Jie-en L., Et al., The relationship between microvessel density, the expression of vascular endothelial growth factor (VEGF), and the extension of nasopharyngeal carcinoma, Laryngoscope, 110, 12, pp. 2066-2069, (2000)

[6]

Khabir A., Karray H., Rodriguez S., Et al., EBV latent membrane protein 1 abundance correlates with patient age but not with metastatic behavior in north African nasopharyngeal carcinomas, Virol J, 2, (2005)

[7]

Kwok Fung Lo A., Liu Y., Wang X., Et al., Identification of downstream target genes of latent membrane protein 1 in nasopharyngeal carcinoma cells by suppression subtractive hybridization, Biochim Biophys Acta, 1520, 2, pp. 131-140, (2001)

[8]

Brahimi-horn C., Pouyssegur J., The role of the hypoxia-inducible factor in tumor metabolism growth and invasion, Bull Cancer, 93, 8, (2006)

[9]

Hui E.P., Chan A.T., Pezzella F., Et al., Coexpression of hypoxia-inducible factors 1alpha and 2alpha, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival, Clin Cancer Res, 8, 8, pp. 2595-2604, (2002)

[10]

Glaser S.L., Hsu J.L., Gulley M.L., Epstein-Barr virus and breast cancer: State of the evidence for viral carcinogenesis, Cancer Epidemiol Biomarkers Prev, 13, 5, pp. 688-697, (2004)

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