Angiogenesis in a T-Lymphoma Growing as a Solid Tumor in Hyperthyroid and Hypothyroid Mice: A Phenomenon Modulated by Thyroid Status

STERLE, H.; VALLI, E.; MARTINEL LAMAS, D.; KLECHA, A.; COLOMBO, L.; MEDINA, V.; CREMASCHI, G.; BARREIRO ARCOS, M.L.

Congreso; The Virtual Congress on Hematology-Age before beaty- An age adjusted approach towards hematological disorders; 2019

Background: Angiogenesis is a physiological process that occurs during embryogenesis, tissue repair, and the development of solid tumors. The thyroid status modulates angiogenesis in various tissues, but its role in tumor angiogenesis has not been elucidated. Objetive: To study the effect of thyroid status on the angiogenesis and proliferation of El-4 T lymphoma growing as a solid tumor in murine models of hyperthyroidism and hypothyroidism. Methods: Female C57BL/6J mice were treated with placebo, with thyroxine (0.012 mg/ml; 30 days) or with propylthiouracil (0.5 mg/ml; 15 days) and were inoculated subcutaneously with EL-4 cells. Tumor volume was measured daily using calipers. The proliferating cell nuclear antigen (PCNA) was quantified by immunostaining and the rate of cell division was determined by staining with CFSE-DA. Vascularization in tumor tissue was evaluated using the Masson?s trichrome staining and immunostaining with an anti-CD31 antibody. Blood vessels supplying the tumor were analized by microscopy. Results: Hyperthyroid animals exhibited a higher tumor volume that was correlated with a higher rate of cell division. Tumor tissue from hyperthyroid mice had increased levels of PCNA expression. Tumors from hyperthyroid animals exhibited more vascularization, with large vessels and increased expression of the vascular endothelium marker CD31. Hyperthyroid mice had a higher level of peritumoral angiogenesis. Tumors from hypothyroid mice did not show significant differences with respect to the controls. Conclusions: The hyperthyroid state induces the growth of new blood vessels that supply the tumor, favoring a greater tumor development. The hypothyroid state has no effect on intratumoral or peritumoral angiogenesis.