Lungs and liver remodeling depends on the presence of metastasis in melanoma B16-bearing mice

DOI: https://doi.org/10.29296/24999490-2022-01-07

N.V. Palkina, D.S. Zemtsov, A.N. Narkevich, Ya.V. Bardetskaya, A.K. Kirichenko, T.G. Ruksha Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1, P. Zeleznyaka str., Krasnoyarsk, 660022, Russian Federation

Pre-metastatic niche formation precedes tumor dissemination although the mechanisms of it remain unclear. Therefore, the aim of the study was to evaluate the expression of molecules characterizing the microenvironment remodeling in target organs lungs and liver, depending on the presence of metastases in murine melanoma B16 in vivo. Material and methods. Melanoma B16 cells transplantation was carried out on C57Bl6 mice followed by the tumor development observation within 15 days. After that the mice were sacrificed. Tumors, lungs and livers tissues were fixed in formalin and embedded in paraffin. Tissues samples were stained with hematoxylin and eosin. Immunohistochemical study was provided with monoclonal antibodies to vascular endothelial growth factor A, smooth muscle actin-α, CD45RО and СD-31. Results. Metastasis were revealed in 33.3% of mice. In mice presented melanoma metastases to visceral organs, an increase in the expression of vascular endothelial growth factor A was found in the lungs, and smooth muscle actin-α and CD31 in the liver, compared with these molecules expression in the group of animals without metastases. Besides, a strong positive correlation between the level of non-proliferating Ki-67-negative melanoma cells in the primary tumor and CD45RO expression in the lungs and liver was observed in metastasis-free animals. Conclusions. The results obtained indicate possible presence of intercellular communication between melanoma cells in the primary tumor and target organs at the premetastatic stage resulting in altering of antitumor resistance
Keywords: 
melanoma, dormant cells, microenvironment, metastasis, Ki-67, VEGFA, SMA, CD45RO, CD31
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