Aging is associated with the accumulation of senescent cells in tissues but also with an increased risk of developing certain cancers. The senescent cell secretome is known to be involved in the development of certain cancers. To study aging and cancer development, skin is a tissue of choice since it is highly exposed to environmental stresses such as solar radiation, which promotes both the development of skin cancers and accelerated skin aging. In this master thesis, the effect of the senescent keratinocyte secretome on the migration of skin cancers was investigated. For this purpose, repeated exposures to UVB were used to induce premature senescence of keratinocytes cultured in monolayer. The induction of senescence was confirmed by the analysis of several biomarkers. Next, the conditioned medium of senescent keratinocytes was used to test its effect on the migration of melanoma and carcinoma cells and showed a slight pro-migratory effect under certain conditions. Analysis of the composition of the secretome of senescent keratinocytes revealed the presence of proteins with a pro-migratory effect. In parallel, a reconstructed epidermis model integrating melanoma cells expressing GFP (green fluorescent protein) was developed to study the interconnection of senescent keratinocytes and melanoma cells in a model closer to in vivo conditions. To induce keratinocyte senescence in reconstructed epidermis, the latter were exposed to UVB or incubated with conditioned medium from senescent keratinocytes.
Study of the impact of UVB-induced senescent keratinocytes on skin cancer cells
Bouriez, I. (Auteur). janv. 2022
Student thesis: Master types › Master en biochimie et biologie moléculaire et cellulaire à finalité approfondie