In vivo STUDIES OF THE EFFECT OF ALPHA-SYNUCLEIN INCORPORATION ON MELANOMA DEVELOPMENT

MALIZIA, FLORENCIA*; ZANOTTI, LUCIA C*; CHAPO, GUSTAVO; MENACHO MÁRQUEZ, MAURICIO

Rosario

Congreso; II REUNIÓN CIENTÍFICA INTERNACIONAL VII REUNIÓN CIENTÍFICA REGIONAL VI CONGRESO NACIONAL DE CIENCIA Y TECNOLOGÍA DE ANIMALES DE LABORATORIO; 2021

Synucleins are a group of neuronal proteins involved in neurodegeneration and cancer. Alpha-synuclein (αS) is the main component of Lewy bodies, the neuropathological hallmark of Parkinson's disease (PD). The mechanisms underlying aggregation, neurotoxicity, and cell-to-cell transmission of αS were explored in depth in this context. Recent evidence suggests that αS plays a role in the pathogenesis of melanoma, the most dangerous form of skin cancer, and a protective role was assigned to this protein in advanced melanoma. However, its role in this type of cancer has not yet been fully explored.Previous results of our group carried out in vitro with melanoma cells showed that they are able to incorporate different aggregation species of αS. These species, not only are non-toxic, but promoted instead proliferation, migration and clonogenic capacity of melanoma cells. In this work, we evaluated in in vivo models the effect of the incorporation of αS fibers on melanoma progression (CICUAL “Characterization of the role of synucleins in different cell types: exploring the relationship between cancer and neurodegenerative diseases”). To explore the impact of αS incorporation on melanoma development, B16-F10 cells (control and previously incubated with αS fibers) were injected subcutaneously below their minimal tumorigenic dose in the right flank in 8-week-old female C57BL/6 mice. (7x104 cells; n = 5/group). Using this approach, we observed that animals injected with pre-treated cells developed tumors within 4 weeks post-inoculation, while no tumor development was observed in control animals at this time. To confirm the role of αS in melanoma growth, 2x105 cells (n = 6/group) were injected as described before. Tumor volume was periodically measured with a caliper during 3 weeks. Growth kinetics indicated that αS treatment significantly promoted tumor growth (P