All-trans retinoic acid and Lapatinib combined treatment impair breast cancer stem cells growth and metastatic potential

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

Congreso; LXV Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2020

Sociedad Argentina de Investigación Clínica (SAIC)

Cancer stem cells (CSC) are resistant to chemo and radiotherapies.To validate CSC as therapeutic targets in breast cancer, we analyzedthe effect of Lapatinib (Lp, HER2 inhibitor), ATRA or the combinedtreatments, on growth, cell cycle distribution and metastaticcapacity of primary mammospheres (CSC enriched cultures) fromHER2 negative cell lines (4T1, MCF-7 and T47D).We determined by WB that HER2 is overexpressed only in CSCsubpopulation of all cell lines analyzed. Primary mammosphereswere treated for 96 h with Lp 1uM for 4T1; 5uM for MCF-7, 2uM forT47D cells combined or not with ATRA 1uM. ATRA treatment aloneor combined with Lp only significantly reduced 4T1 mammospheresdiameters and signs of cell death were also observed.The combined treatment induced cell cycle arrest at G0/G1 phaseafter 48h of treatment in 4T1 mammospheres, analyzed by flowcytometry. However, this combination not significantly induces cellcycle arrest in MCF-7 mammospheres. Finally, we performed anexperimental lung metastasis assay in mice pretreated with ATRAand Lp and observed that combination reduced metastatic potentialof 4T1 cells derived from mammospheres.In the present work we have demonstrated that the CSC componentof HER2 negative cell lines overexpress such receptor. Moreover,Lp and ATRA combined treatment can successfully reduce mammospheres growth and metastatic potential in 4T1 experimental model.