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

• Published in: Archives of virology Vol. 164; no. 5; pp. 1343 - 1351
• Main Authors: Mori, Hiroshi, Tomiyasu, Takafumi, Nishiyama, Kanako, Matsumoto, Maiko, Osawa, Yoshiaki, Okazaki, Katsunori
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.05.2019; Springer Nature B.V
• Subjects: Amino acids; Angiogenesis; Biomedical and Life Sciences; Biomedicine; blood vessels; Bovine leukemia virus; Bovine leukosis; carcinogenesis; cattle; cell lines; chemoattractants; Chemotaxis; Endothelial cells; fibroblasts; human umbilical vein endothelial cells; Infectious Diseases; Leukemia; Leukemogenesis; Lymphoma; Medical Microbiology; mice; mutation; neoplasm cells; neoplasms; Original Article; Progenitor cells; rats; Stem cells; Tax protein; Tumorigenesis; Tumors; Umbilical vein; Vascularization; Virology; viruses; Xenografts
• ISSN: 0304-8608; 1432-8798; 1432-8798
• DOI: 10.1007/s00705-019-04191-3

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.