Relationship between eukaryotic translation initiation factor 4E and malignant angiogenesis in non-hodgkin lymphoma

Abstract

The relationship between angiogenesis and eukaryotic translation initiation factor 4E (EIF4E) expression level in non-Hodgkin lymphoma (NHL) was studied. Mean microvessel density (MVD) and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3. 1 (+) and transfected into Raji cells. A series of angiogenesis related factors, including vascular endothelial growth factor (VEGF), matrix metalloproteinases 9 (MMP-9) and tissue inhibitor of metalloproteinases-2 (TIMP-2) proteins were detected by Western blot. The results showed that: (1) The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas (P<0.05) and the expression of EIF4E was positively correlated with MVD in lymph node of NHL (r=0.695,P<0.01). (2) Antisense EIF4E eukaryocytic expression vector (pcDNA3. 1-EIF4Eas) was constructed successfully. (3) EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells (NHPMC), and blockage of EIF4E expression brought down the expression of VEGF and MMP-9. However, TIMP-2 was undetectable in Raji cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL.

Keywords

eukaryotic translation initiation factor 4E / non-Hodgkin lymphoma / matrix metalloproteinases 9 / tissue inhibitor of metalloproteinases-2

References

[1] HazarB, PaydasS, ZorludemirS, et al. . Prognostic significance of microvessel density and vascular endothelial growth factor (VEGF) expression in non-Hodgkin's lymphoma. Leuk Lymphoma, 2003, 44: 2089-2089

[2] JoshiB, CamerronA, JagusR. Characterization of mammalian eIF4E-family members. Eur J Biochem, 2004, 271: 2189-2189

[3] De BenedettiA, GraffJ R. eIF-4E expression and its role in malignancies and metastases. Oncogene, 2004, 23: 3189-3189

[4] WangS, RosenwaldI B, HutzlerM J, et al. . Expression of the eukaryotic translation initiation factors 4E and 2alpha in non-Hodgkin's lymphomas. Am J Pathol, 1999, 155: 247-247

[5] HennessyB T, HanrahanE O, DalyP A. Non-Hodgkin lymphoma: an update. Lancet Oncol, 2004, 5: 341-341

[6] BratthauerG L. The avidin-biotin complex (ABC) method and other avidin-biotin binding methods. Methods Mol Biol, 1999, 115: 203-203

[7] ZheniloS, DeyevI, SerouS, et al. . Regulation of oct-1 gene transcription is different in lymphoid and non-lymphoid cells. Biochimie, 2003, 85: 715-715

[8] HicklinD J, EllisL M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol, 2005, 23: 1011-1011

[9] KossakowskaA E, UrbanskiS J, Janowska-WieczorekA. Matrix metalloproteinases and their tissue inhibitors —expression, role and regulation in human malignant non-Hodgkin's lymphomas. Leuk Lymphoma, 2000, 39: 485-485

[10] SeoD W, LiH, GuedezL, et al. . TIMP-2 mediated inhibition of angiogenesis: an MMP-independent mechanism. Cell, 2003, 114: 171-171