6. Unraveling the role of CLCA2 during the in situ to invasive transition in breast cancer

NAIARA RODRIGUEZ PADILLA ,; MARIANELA SCIACCA, ; MARÍA DEL PILAR CARBALLO ,; EZEQUIEL LACUNZA,; MARTIN ABBA, ; LINA MARINO , ; ÉRICA ROJAS BILBAO ,; MARCELA VILLAVERDE, ; PABLO SAEZ , ; ANA MARIA EIJAN; CATALINA LODILLINSKY

Congreso; Reunion Anual de Sociedades de Biociencias; 2023

SAIC

Ductal carcinoma in situ (DCIS) in breast cancer (BC) is defined as a proliferation of epithelial neoplastic cells contained within the lumen of mammary ducts. DCIS are the precursors of infiltrating carcinomas (IDC) but it is not yet possible to predict which or when they will progress to more advanced stages.Intraductal inoculation of human MCF10DCIS.com cells into the murine mammary gland generates DCIS that spontaneously progress to IDC. We have shown that MT1-MMP, a membrane metalloprotease with collagenase activity, is essential for the DCIS to IDC transition. In the invasive state, MT1-MMP is over-expressed at the invasion front, defining two cell populations: MT1-MMPhigh and MT1-MMPlow. The transcriptome analyses of these populations was compared against a set of human high-grade DCIS. Chloride Channel Accessory 2 (CLCA2) is overexpressed, in both, worse prognosis-human DCIS and MT1-MMPhigh population, which suggests that this gene is involved in the early transition of BC. CLCA2 expression was assayed by immunofluorescence analyses on paraffin sections of invasive tumor obtained after intraductal injection of tumor cells. We observed an increase in expression in the peripheral areas as well as in contact with the stroma, similarly to MT1-MMP.CLCA2 protein levels in BC were assayed by IHC in a cohort of patients (n=58). The H-score (% of labeled cells multiplied the intensity of the label) for CLCA2 was higher in DCIS vs to normal tissues (p