GIADA PONTECORVI

Dottoressa

ciclo: XXXIII



Titolo della tesi: Antitumoral activity of the Estrogen Receptor β agonist LY500307 against melanoma and new nanocarrier strategy for its pharmacological delivery

Worldwide the total incidence of cutaneous melanoma is higher in men than in women. In addition, localized melanomas had a lower propensity to metastasize in women, resulting in a better survival when compared with men. Although we still lack conclusive data explaining these differences, among others factors, a fundamental role appears played by sex hormones, suggesting a protective effect of estrogens. However, conflicting results exist about the beneficial action of estradiol and its analogues, at least in part related to the different action of Estrogen Receptors (ERs) α and β, favoring proliferation the former and exerting an antitumor function the latter. Here we investigated the effects of estrogen treatments as well as those of the ERβ specific agonist LY500307 in a series of melanoma cell lines characterized by different genetic background and stages. Our results showed that melanoma in vitro treatment with LY500307 induced a significant cell cycle accumulation at the G2/M boundary associated with anomalous mitotic structures and increased pro-apoptotic signals. Moreover, LY500307 treatment was able to decrease melanoma cell malignancy reducing in vitro cell migration and down-regulating the expression of some oncomiRs belonging to the miR-17 family. In view of LY500307 promising results and in order to exploit these studies on melanoma in vivo, we focused on the innovative therapeutic approach of nanocarrier-based drugs delivery. Since we previously unveiled the roles of oleic acid (OA) against melanoma in in vitro studies (Bellenghi M. et al, 2015; Puglisi R. et al, 2018), we generated OA-based nanovesicles according to a nanoemulsion formulation. After evaluating some key properties of these nanovesicles (i.e. size, stability), we confirmed their good uptake through a Nile Red staining in metastatic melanoma, and any effect on normal cell viability. Although in vivo studies in proper animal models should be run before any possible clinical translation, these results allowed hypothesizing the in vivo long-term therapeutic potential of these OA-nanovesicles loaded with LY500307. Indeed, as these vehicles can combine the anticancer drug-associated specificity with reduced side effects, OA-based nanoemulsions could represent a possible future strategy to fight cancer, including melanoma.

Produzione scientifica

  • 11573/1175916 - 2018 - SCD5 restored expression favors differentiation and epithelial-mesenchymal reversion in advanced melanoma (01a Articolo in rivista)
    PUGLISI, ROSSELLA; BELLENGHI, MARIA; PONTECORVI, GIADA
  • 11573/1338856 - 2019 - Role of Estrogen receptor β against melanoma progression (04f Poster)
    PONTECORVI, GIADA; BELLENGHI, MARIA; TIRELLI, VALENTINA
  • 11573/1338848 - 2019 - NRAS-mutated melanoma cell lines are susceptible to G2/M blockage and cell death activation in response to estrogen treatment (04d Abstract in atti di convegno)
    PONTECORVI, GIADA; BELLENGHI, MARIA; TIRELLI, VALENTINA
  • 11573/1337972 - 2019 - On exosome functional role in cancer. miR-494 complex regulation in melanoma cells and corresponding exosomes (01b Commento, Erratum, Replica e simili)
    BELLENGHI, MARIA; PONTECORVI, GIADA
  • 11573/1337953 - 2019 - Autoantibodies specific to ERa are involved in tamoxifen resistance in hormone receptor positive breast cancer (01a Articolo in rivista)
    PUGLISI, ROSSELLA; PONTECORVI, GIADA; CIRULLI, FRANCESCA; PIZZUTI, LAURA; BARBA, MADDALENA
  • 11573/1364196 - 2020 - Tumor-derived extracellular vesicles and microRNAs: functional roles, diagnostic, prognostic and therapeutic options (01g Articolo di rassegna (Review))
    PONTECORVI, GIADA; BELLENGHI, MARIA
  • 11573/1433804 - 2020 - Sex and gender disparities in melanoma (01g Articolo di rassegna (Review))
    BELLENGHI, MARIA; PUGLISI, ROSSELLA; PONTECORVI, GIADA; DE FEO, ALESSANDRA
  • 11573/1420367 - 2020 - Circulating miR34a levels as a potential biomarker in the follow-up of Ewing sarcoma (01a Articolo in rivista)
    DE FEO, ALESSANDRA; PONTECORVI, GIADA
  • 11573/1433802 - 2020 - microRNAs as new possible actors in gender disparities of Covid-19 pandemic (01m Editorial/Introduzione in rivista)
    PONTECORVI, GIADA; BELLENGHI, MARIA
  • 11573/1661541 - 2021 - A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers (01g Articolo di rassegna (Review))
    BELLENGHI, MARIA; MANZINI, VALERIA; PONTECORVI, GIADA; ORTONA, ELENA

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