Evaluation of the promotion of pro-metastatic capacities mediated by sEVs secreted by MDA-MB-231 metastatic breast cancer cells and identification of “EMT-promoter” sEV-miRs present in their cargo
Date
2023
Type:
Thesis
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143 p.
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Authors
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Publisher
Universidad del Desarrollo. Facultad de Medicina
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Abstract
Breast cancer (BC) is one of the most common and deathly cancers worldwide.
However, despite the improvements in screening and treatment, there is a high probability of local recurrence and distant metastasis to occur; the latter being the main cause of the patient’s death. Communication between heterogeneous tumor cells mediated by small extracellular vesicles (sEVs) is essential to promote tumorigenesis and metastasis. sEVs are nanosized vesicles secreted by all cell types that mediate intercellular communication through their cargo, which include nucleic acids, proteins and other biomolecules. However, the mechanisms and specific molecules involved in these phenomena are still not completely defined and vary between different cancer types. Among the molecules described in the cargo of sEVs are microRNAs (sEV-miRs); small non-coding, single-stranded RNA molecules of approximately 20 nucleotides, which are master regulators of gene expression. It is widely demonstrated that cellular miRNA dysregulation can promote tumor growth, progression and metastasis. These findings have positioned miRNAs, and particularly sEV-miRs as a new research focus worldwide. Epithelial-mesenchymal transition (EMT) is a complex and dynamic process that involves many cellular and molecular changes. Cells undergoing EMT can increase their tumorigenic and pro-metastatic capacities, such as cell migration and invasion, cytoskeleton remodeling, increased anchorageindependent growth, among others. Some miRNAs have been implicated in the regulation of EMT in BC, such as members of the let-7 and miR-200 family, as well as miR-105, miR-21 and miR-10b. However, to date there are very few studies that consider BC tumor cells-secreted sEVs as vehicles for “EMTpromoter” sEV-miRs, favoring the EMT and EMT-related phenotypic and functional changes (such as increased migration), promoting the tumorigenic and/or metastatic potential of recipient cells. Therefore, we hypothesize that the
EMT and the migration of cells with no metastatic potential is favored by specific sEV-miRs in the cargo of metastatic BC cell-secreted sEVs. The aim of this project is to characterize the sEV-miRs profile of metastatic BC cells and identify specific sEV-miRs that could induce EMT and/or migration in cells with no metastatic potential. The findings of this thesis could be relevant in order to identify new possible BC biomarkers in sEVs, as well as the possible use of specific sEV-miRs as therapeutic options to treat this disease.
Description
Thesis presented to the Faculty of Medicine of Universidad del Desarrollo, to opt the academic degree of Doctor in Science and Innovation in Medicine
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Citation
Keywords
090036S, Breast cancer, Extracellular vesicles, miRNAs