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Role of Vascular Endothelial Growth Factor (VEGF) in Thymus of Mice under Normal Conditions and with Tumor Growth

E. P. Kisseleva1*, A. V. Krylov1, I. V. Lyamina1, I. V. Kudryavtsev1,2, and V. I. Lioudyno1

1Institute for Experimental Medicine, 197376 St. Petersburg, Russia; fax: +7 (812) 234-9489; E-mail: ekissele@yandex.ru

2School of Biomedicine, Far Eastern Federal University, 690091 Vladivostok, Russia; fax: +7 (423) 243-2315; E-mail: rectorat@dvfu.ru

* To whom correspondence should be addressed.

Received August 24, 2015; Revision received December 1, 2015
In our study, we for the first time investigated a role for VEGF as a factor regulating transendothelial migration of murine thymocytes in vitro. Effects of VEGF were examined in a model of thymocyte migration across a monolayer of EA.hy 926 endothelial cells. We showed that VEGF enhanced transendothelial migration of murine thymocytes and their adhesion to endothelial cells in a dose-dependent manner. VEGF did not influence thymocytes, but rather acted on endothelial cells by upregulating surface expression of adhesion molecule ICAM-1 and downregulating activity of 5′-nucleotidase. Effects from VEGF were comparable with those from TNF-α. Because it is known that administration of VEGF to intact animals results in thymic atrophy, it was assumed that it might play a role in developing thymic involution during tumor growth. Enhanced egress of thymocytes to the periphery was considered as a plausible mechanism underlying effects of VEGF. However, we revealed no difference in parameters of in vitro transendothelial migration for thymocytes from animals bearing a transplantable hepatoma 22a compared to control animals. VEGF mRNA expression in lysates of thymic stroma was found to be upregulated in mice with grafted tumors, whereas at the protein level the amount of VEGF did not differ. While examining expression of VEGF receptors on thymocytes by flow cytometry, both VEGFR-1 and VEGFR-2 were not detected, whereas the percentage of Nrp-1-positive thymocytes in animals with hepatoma 22a was as high as in the control group. Thus, we were unable to confirm a hypothesis regarding participation of VEGF in developing thymic involution during progression of experimental hepatoma. However, a set of novel data concerning a role for VEGF in stimulating transendothelial migration of thymocytes in vitro was obtained, and it may be of significance for understanding mechanisms underlying thymus functioning as well as a role of this cytokine in preparing endothelial cells for egress of thymocytes to the periphery.
KEY WORDS: thymus, vascular endothelial growth factor (VEGF), migration, adhesion, endothelial cells, VEGF receptors, activity of 5′-nucleotidase

DOI: 10.1134/S0006297916050060