Cadherin switching as prognostic biomarker for bladder cancer

Anno
2017
Proponente -
Struttura
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca
Componente Qualifica Struttura Categoria
Cristina Raimondi Borsiste Sapienza Università di Roma - Dipartimento di Medicina Molecolare, Unità di Ricerca Cellule Tumorali Circolanti Altro personale Sapienza o esterni
Abstract

E-cadherin is expressed by many normal tissues and is the main mediator of cell-cell adhesion mediated by the cadherin cell adhesion molecules. Considering these actions on epithelial polarity it can be considered as a tumor suppressor. N-cadherin in normal condition is not expressed by epithelial tissues. In advanced cancers, tumor progressions or metastatic settings it is reported an increase in N-cadherin that is accompanied by a decrease in E-cadherin. This phenomena is known as cadherin switching (CS).
Our research will focus on bladder cancer and we'll analyze both tumor tissue samples and liquid biopsy samples (circulating tumor cells).
Patients with histologically confirmed diagnosis of bladder cancer will be divided in three groups in accordance with tumor characteristics: non-muscle invasive tumors (Ta-1 N0 M0), muscle invasive tumors (T2-4 N0 M0) and metastatic muscle invasive tumors (T2-4 N1-3 or M1).
Tumor tissue analysis: formalin-fixed, paraffin-embedded tumor samples will be used to evaluate DAPI, GATA3, E-cadherin and N-cadherin in tumor tissue.
Liquid biopsy analysis: peripheral blood will be collected at the time of patients enrollment and 1 hour before main surgery. First 3 mL of blood sample will be incubated with 4 mL of ScreenCell FC buffer, containing red blood cell lysis and fixation buffer; 30% NaOH will be added until a pH of around 7. Seven mL of diluted blood will be transferred into device tank and filtered using a vacutainer tube. After washing with 1.6 mL of PBS to remove red blood cells debris, the filter will be released on absorbing paper. The ScreenCell® Cyto filter is released into a standard microscopy glass slide and cytological/ immunocytochemical studies can be conducted directly on the filter using 4 markers: GATA3, DAPI, E-cadherin and N-cadherin.
Difference in these markers expression and cadherin switching will be reported and compared in accordance with different groups.

ERC
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