INVESTIGATION OF THE ROLE OF SEMAPHORIN 3A IN THE THYMUS AT NORMAL CONDITIONS AND TUMOR GROWTH

Abstract

Semaphorin 3A (Sema3A) an axon guidance factor also possesses some immunomodulatory activity. It is known to be produced by human thymic epithelial cells and to reveal chemorepellent activity towards human thymocytes. The aim of the study was to investigate the expression of Sema 3A and its receptors in murine thymus as well as to assess their changes during experimental tumor growth. With the help of Reverse Transcription-PCR assay we showed that Sema 3A mRNA was expressed in the thymus of intact mice and in thymocytes mRNA of the following Sema 3A receptors: Neuropilin-1, Plexins A1-A3 were expressed in thymocytes and no Plexin A4 mRNA. Sema 3A revealed its chemorepellent effect towards murine thymocytes in vitro and this effect was mediated via Neuropilin-1 receptor. Sema 3A did not influence thymocyte adhesion and their transmigration across the monolayer of to endothelial EA.hy926 cell line. We hypothesized that Sema 3A may enhance thymocyte egress to periphery and be responsible for the development of thymic involution during tumor growth. But we were not able to show any difference in the protein Sema 3A level in thymic stroma between hepatoma 22a-bearing mice and control animals, as well as no significant difference in the percentage of Neuropilin-1 positive thymocytes during tumor growth. The data obtained do not support the initial idea of Sema 3A participation via its chemorepellent activity in the enhancement of thymocyte egress to periphery during tumor growth.