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Archives of Virology

, Volume 164, Issue 5, pp 1343–1351 | Cite as

L233P mutation in the bovine leukemia virus Tax protein depresses endothelial cell recruitment and tumorigenesis in athymic nude mice

  • Hiroshi Mori
  • Takafumi Tomiyasu
  • Kanako Nishiyama
  • Maiko Matsumoto
  • Yoshiaki Osawa
  • Katsunori OkazakiEmail author
Original Article
  • 63 Downloads

Abstract

Bovine leukemia virus (BLV) can be divided into two categories based on the amino acid at position 233 in the Tax protein, which probably plays a crucial role in leukemogenesis. We show here that a rat fibroblast cell line stably expressing L233-Tax formed significantly larger tumors than P233-Tax-expressing cells in a murine xenograft study. Although the microvessel density was comparable in both tumors, visible blood vessel invasion was observed only on tumors from L233-Tax-expressing cells. Endothelial cell tube formation assays using human umbilical vein endothelial cells showed no significant difference in angiogenic activity between conditioned medium from L233- and P233-Tax-expressing cells, whereas in vitro chemotaxis assays revealed that only L233-Tax-expressing cells produced a chemoattractant for endothelial cells. Since pathological neovascularization can occur from the recruitment of endothelial progenitor cells, these results suggest that L233-Tax-expressing cells recruit murine endothelial progenitor cells and promote neovascularization to support tumor growth. BLV-infected lymphoma cells may also recruit bovine endothelial progenitor cells to promote neovascularization. The findings of this study are consistent with our previous observation that BLV carrying P233-Tax has a significantly longer incubation period for developing tumors than the virus carrying L233-Tax and provide insight into the function of Tax in leukemogenesis by BLV.

Abbreviations

BLV

Bovine leukemia virus

HTLV

Human T-lymphotropic virus

EBL

Enzootic bovine leucosis

LTR

Long terminal repeat

ATL

Adult T-cell leukemia

HBZ

HTLV-1 basic leucine zipper factor

CT

Threshold cycle

MVD

Microvessel density

CM

Conditioned media

HUVEC

Human umbilical vein endothelial cell

DMEM

Dulbecco’s modified Eagle’s medium

RFU

Relative firefly luciferase unit

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

H-DME

Ham’s F12 medium:DMEM (1:1)

Notes

Acknowledgements

We would like to thank Sapporo General Pathology Laboratory for immunohistochemical staining. We also thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Funding

This work was supported in part by grants from the Project of the NARO Bio-Oriented Technology Research Advancement Institution (the special scheme project on vitalizing management entities of agriculture, forestry and fisheries) [grant number 16930291] and by the Ministry of Education, Culture, Sports, Science and Technology of Japan [grant numbers 24580451, 16K08060] to KO.

Compliance with ethical standards

Conflicts of interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Immunology and Microbiology, Faculty of Pharmaceutical SciencesHealth Sciences University of HokkaidoHokkaidoJapan

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