Evidence for Enhanced Exosome Production in Aromatase Inhibitor-Resistant Breast Cancer Cells
| Autor: | Giusi La Camera, Catia Morelli, Stefania Catalano, Salvatore Panza, Ines Barone, Giuseppina Augimeri, Diego Sisci, Balázs Győrffy, Cinzia Giordano, Sebastiano Andò, Daniela Bonofiglio, Luca Gelsomino |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proteomics
medicine.drug_class Breast Neoplasms GTPase exosomes Exosome Catalysis Inorganic Chemistry endocrine resistance lcsh:Chemistry Breast cancer breast cancer medicine Cluster Analysis Humans Physical and Theoretical Chemistry Aromatase skin and connective tissue diseases Molecular Biology lcsh:QH301-705.5 Spectroscopy Aromatase inhibitor biology Aromatase Inhibitors Communication Organic Chemistry Rab GTPases Cancer Estrogens General Medicine medicine.disease Microvesicles Up-Regulation Computer Science Applications Gene Expression Regulation Neoplastic lcsh:Biology (General) lcsh:QD1-999 Drug Resistance Neoplasm rab GTP-Binding Proteins MCF-7 Cells biology.protein Cancer research Female Rab |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 5841, p 5841 (2020) International Journal of Molecular Sciences |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Aromatase inhibitors (AIs) represent the standard anti-hormonal therapy for post-menopausal estrogen receptor-positive breast cancer, but their efficacy is limited by the emergence of AI resistance (AIR). Exosomes act as vehicles to engender cancer progression and drug resistance. The goal of this work was to study exosome contribution in AIR mechanisms, using estrogen-dependent MCF-7 breast cancer cells as models and MCF-7 LTED (Long-Term Estrogen Deprived) subline, modeling AIR. We found that exosome secretion was significantly increased in MCF-7 LTED cells compared to MCF-7 cells. MCF-7 LTED cells also exhibited a higher amount of exosomal RNA and proteins than MCF-7 cells. Proteomic analysis revealed significant alterations in the cellular proteome. Indeed, we showed an enrichment of proteins frequently identified in exosomes in MCF-7 LTED cells. The most up-regulated proteins in MCF-7 LTED cells were represented by Rab GTPases, important vesicle transport-regulators in cancer, that are significantly mapped in “small GTPase-mediated signal transduction”, “protein transport” and “vesicle-mediated transport” Gene Ontology categories. Expression of selected Rab GTPases was validated by immunoblotting. Collectively, we evidence, for the first time, that AIR breast cancer cells display an increased capability to release exosomes, which may be associated with an enhanced Rab GTPase expression. These data provide the rationale for further studies directed at clarifying exosome’s role on endocrine therapy, with the aim to offer relevant markers and druggable therapeutic targets for the management of hormone-resistant breast cancers. |
| Databáze: | OpenAIRE |
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