26/09-2022 - Catalina LODILLINSKY : New biomarkers as putative predictors of early progression in breast cancer

21 - Septembre - 2022

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 13h–14h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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LUNDI 26 SEPTEMBRE 2022

New biomarkers as putative predictors of early progression in breast cancer

Catalina LODILLINSKY

Chercheur statutaire au CONICET, Instituto de Oncologia "Ángel H. Roffo", Buenos Aires, Argentine

invitée par Equipe de Céline PRUNIER, (Equipe PRUNIER (mathieu.boissan@inserm.fr))

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Ductal carcinoma in situ (DCIS) in breast cancer is defined as a proliferation of epithelial neoplastic cells contained within the lumen of mammary ducts. Currently, evidence suggests that in situ tumors are precursors of invasive tumors, but progression markers are not yet available.
We have previously demonstrated using the intraductal xenograft model that membrane-type 1 matrix metalloproteinase (MT1-MMP) is essential for the transition from in situ to invasive tumors. Subsequently, we have completed RNAseq analysis (Illumina HISeqTM) based on differential MT1-MMP expression (MT1-MMPhigh vs MT1-MMPlow) where we identified 47 differentially expressed genes. A Molecular Portrait of High-Grade DCIS was previously performed (Abba, 2015). When we compared their genetic profile against the MT1-MMPhigh population, we found up-regulated SPARC, PTGS2, and CLCA2 only in the more aggressive group (DCIS-C1) and in the MT1-MMPhigh cell population, highlighting them as promising targets in early breast cancer progression.
SPARC expression was analyzed in a breast tumors cohort with in situ features obtained in the Pathology Department of the Institute of Oncology A. H. Roffo (n=60). We observed that SPARC expression was higher in tumors with worse prognosis and nuclear grade III. We also found a positive correlation between SPARC and MT1-MMP expression in 1217 breast cancer samples (TCGA), and an increase in SPARC expression in tumor and metastatic tissues compared to normal tissue.
When SPARC is knocking down in LM38-LP cell line the MT1-MMP-dependent capacity of gelatin degradation is reduced demonstrating the pro-invasive role of SPARC.
Our results suggest that SPARC should be considered as a pro-tumoral marker of early breast cancer progression making them a crucial factor for the development of personalized medicine.

 

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