Effect Lapatinib and all trans Retinoic Acid (ATRA) combined treatment on mammary cancer stem cells derived from HER2 negative cell lines

AGUSTINA TARUSELLI; ANDRES BECHIS; LIZETH ARIZA BAREÑO; MARIA J. COSTA; ALEJANDRO J. URTREGER; LAURA B. TODARO

Mar del Plata

Congreso; LXIII Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Sociedad Argentina de Investigación Clínica (SAIC)

Cancer stem cells (CSC) are resistant to both chemo and radiotherapies and are also considered as the metastasis seed. In order to validate CSC as new therapeutic targets in breast cancer, we have analyzed whether the CSC component of three HER2 negative cell lines (4T1, MCF-7 and T47D) express this receptor and which is the effect of Lapatinib (Lp, HER2 inhibitor) and ATRA (Vitamine A active metabolite) or the combined treatments, on the growth and development of primary mammospheres (CSC enriched cultures).HER2 expression was analyzed by Western blot and immunofluorescence using monolayers and primary mammospheres from 4T1, MCF7 and T47D cell lines. We have determined that HER2 is overexpressed only in the CSC subpopulation of all the analyzed cell cultures. Moreover, primary mammospheres were treated for 96 h with Lp1µM for 4T1 cells; 5µM for MCF-7, 2µM for T47D cells combined or not with ATRA 1µM. Although we have previously shown that ATRA did not induced 4T1 growth inhibition, the treatment with ATRA alone or combined with Lp significantly reduced the diameter of 4T1 mammospheres. Important signs of cell death were also observed in the combined treatment condition. Similar results were obtained in MCF-7 and T47D cell lines (NS).In the present work we have demonstrated that the CSC component of HER2 negative cell lines overexpress such receptor. Moreover, the Lp and ATRA combined treatment can successfully reduce mammospheres growth. Our work provides for the first-time in vitro evidences for the potential use of the Lapatinib and ATRA combined therapy in HER2 negative tumors, having as main target the stem component.