The thyroid status modulates the development of murine T lymphoma line EL-4 growing in vivo as a solid tumor in syngeneic mice

STERLE H.A.; VALLI E; CAYROL F; COLOMBO L; CREMASCHI G A; BARREIRO ARCOS M L

Dresden

Congreso; 8th Congress of the International Society for NeuroimmunoModulation (ISNIM) together with the German Endocrine-Brain-Immune Network (GEBIN); 2011

ISNIM and GEBIN

The thyroid status modulates the development of murine T lymphoma line EL-4 growing in vivo as a solid tumor in syngeneic mice. HA Sterle1, E Valli1, F Cayrol1, L Colombo2, GA Cremaschi1,3, ML Barreiro Arcos1. 1CEFYBO-CONICET-UBA, 2Instituto de Oncología A,H Roffo, 3FFyB-UBA. Buenos Aires, Argentina. We have shown that thyroid hormones(THs)are able to regulate proliferation of T cells and demonstrated their influence on tumor development. Our aim was to evaluate the effect of THs on the development of a T lymphoma. For this purpose we developed murine models of hiper- and hypothyroidism in C57BL/Hep mice, which were inoculated with EL-4 cells to develop solid tumors. No differences were found between these groups in regard to the tumor latencies. However, hyperthyroid mice displayed a higher rate of tumor growth and an increased tumor volume than euthyroid animals. In contrast, hypothyroid mice showed a lower tumor growth than controls, but they developed more kidney metastasis than eu-or hyperthyroid mice. The expression of cell cycle regulatory proteins in solid tumors was analyzed by qPCR. Increased expression of cyclins A2, D1, D3 and E1 and decreased levels of p21 and p27 were found in hyperthyroid mice, while hypothyroid animals showed no significant differences in the cyclin mRNA levels, but they displayed increased expression of p27. Genomic expression of Rb in solid tumors was not modulated by the thyroid status, but metalloprotease 2 and 9 mRNAs were increased only in the hyperthyroid state. On the other hand, we tested the modulation of the thyroid status on the immune system functionality. In vitro mitogen induced proliferative responses of T and B cells from hyperthyroid mice were higher than controls, while they were lower in the hypothytroid animals. Also higher and lower NK cell activities were found in hyper- and hypothyroid mice, respectively, compared to controls. These results suggest that thyroid status is able to modulate the tumor growth through the regulation of proteins involved in the progression and/or arrest of the cell cycle, the modulation of metalloproteases expression that could contribute to angiogenesis, and through the regulation of the immune cell function that could limit the generation of metastases.