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Characterization of proteins involved in intracellular pathways distinctive for colon cancer stem cells

The aim of this thesis is to use a differential proteomic approach to study protein expression changes (up- or down- regulation) in colon cancer stem cells (CD133+ cells) compared to colon cancer differentiated cells (CD133- cells), isolated from a colorectal carcinoma cell line. This comparison was performed through the use of the 2D-DIGE methodology (Yan et al., 2002; Alban et al., 2003). In particular we analyzed protein expression in a colon cancer cell line Caco-2 available at CEINGE cell bank. CSCs have been separated from differentiated cancer cells by flow cytometry using CD133 as stemness marker.
Expanding evidence highlights the role of CD133 as a marker of CSCs in various human tumours. CD133 was expressed in combination with CD44+ in approximately 0.1% of cells within a large series of prostate tumours, irrespective of their grade or metastatic state. These cells were capable of selfrenewal, proliferation, and multi-lineage differentiation in vitro to recapitulate the original tumour phenotype, consistent with CSC properties (Collins et al., 2005). In fact, CSCs are significantly enriched in CD133+ subpopulations derived from human colon cancer and hepatocellular carcinomas, as shown by their potential to both self-renew and differentiate, to form colonies and proliferate in vitro, and by their ability to reform the original tumour phenotype when transplanted either subcutaneously or into the renal capsule of immunodeficient mice (O’Brien et al., 2007; Suetsugu et al., 2006).

Mostra/Nascondi contenuto.
6 1. INTRODUCTION 1.1 Normal adult stem cells and cancer stem cells Normal adult stem cells are specific to tissue and organ type. They form only a small fraction of total cell population and can proliferate over the life time of the organism (Boman et al., 2007). These cells, relatively undifferentiated and slowly dividing, are responsible for maintaining tissue integrity and generating of new cells (McDonald et al., 2006; Boman et al., 2007). They are most commonly found in the bone marrow, where they give rise to the different blood cells, but the stem cells also reside within liver, stomach, and colon (Gang-Ming-Zou., 2008). The progeny of normal adult stem cells, is more differentiated and divides faster then their progenitors. According to recent literature (Boman et al., 2007; Potten et al., 1997), the main features of adult stem cells are: - self-renewal (a process by which a daughter cell maintains the same properties of its parent cell); - plasticity (a tissue-specific stem cell’s ability to differentiate into a cell of an other different tissue); - potential for multilineage differentiation; - tissue regeneration. Stem cells can divide with symmetric or asymmetric division (fig.1).

Tesi di Laurea Magistrale

Facoltà: Scienze Biotecnologiche

Autore: Lidia D'alò Contatta »

Composta da 109 pagine.

 

Questa tesi ha raggiunto 109 click dal 01/10/2010.

Disponibile in PDF, la consultazione è esclusivamente in formato digitale.