|Tipo di tesi||Tesi di laurea magistrale|
|Titolo||Interazione fra cellule Mesenchimali Stromali e Sarcoma di Ewing: dallo studio del microambiente tumorale all'approccio terapeutico|
|Titolo in inglese||Mesenchymal Stromal Cells Interaction With Ewing Sarcoma: Between Insights on Tumor Microenvironment and a Therapeutic Strategy|
|Struttura||Dipartimento di Scienze della Vita|
|Corso di studi||BIOTECNOLOGIE MEDICHE E FARMACEUTICHE (D.M. 270/04)|
|Data inizio appello||2014-12-10|
|Disponibilità||Accessibile via web (tutti i file della tesi sono accessibili)|
Il microambiente tumorale, anche noto come stroma tumorale (ST) è una struttura complessa all’interno della quale cellule non trasformate, quali cellule del sistema immunitario, cellule dei vasi sanguigni e fibroblasti interagiscono intimamente con la componente tumorale. Uno degli elementi cellulari più rappresentati all’interno di questo complesso mosaico, è costituito dai cosiddetti fibroblasti associati al tumore (TAF).
Tumor microenvironment, also referred as tumor stroma (TS), is a composite structure made by non-transformed and malignant elements. Inside this heterogeneous mosaic, different cellular elements including immune cells, fibroblasts and blood vessel cells reside in close proximity and strictly interact with tumor compartment. The most prominent component of TS is represented by tumor-associated fibroblasts (TAF). In recent years, TAF acquired growing interest because of the evidences on its influence on cancer initiation, development and metastatization. Currently, many studies have suggested that tumor progression and maintenance may be promoted by the cross-talk between tumor and the surrounding TAF, through cell-to-cell contact and/or secreted molecules. Even large amount of data confirmed the supportive role played by TAF in tumor growth, their ontogeny remains still debated. Some studies have identified the local fibroblasts as the major source of TAF. However, many evidences showed that mesenchymal progenitor cells (MSC), derived from bone marrow or adipose tissue and attracted into tumor burden by cytokines and chemotactic factors released by tumor itself, could also be included into TAF population, taking part into tumor microenvironment. Ewing’s sarcoma (ES) represents a unique model to better understand the relationship between tumor cells and MSC. Recent findings have suggested that, this tumor could originate from transformed stem cells of mesenchymal origin; in addition MSC have been isolated from sarcoma specimens, demonstrating their active role in tumor stroma formation. Starting from these assumptions, we here attempted to better clarify biological effect of the cellular interplay between MSC and ES cells. In this study we first assessed the effects displayed by adipose derived (AD)-MSC on ES cells growth. Then, the pro-migratory effect of exerted by ES on AD-MSC was studied by transwell assays and time lapses. Since MSC have been proven to effectively vehicle anti-cancer agents, in this thesis we additionally investigated the effectiveness of combinatory approach based on MSC and anticancer molecule, such as TRAIL, to induce apoptosis on ES cells, providing further insights for a cell based cancer therapy for sarcoma.