Effect of retinoids and lapatinib treatments on differentiation and metastatic capacity of cancer stem cells in a murine mammary triple negative cell line

AGUSTINA TARUSELLI; ANDRES BECHIS; MARIA J. COSTA; LUCIA CANEDO; CAROLINA PEREZ CASTRO; ALEJANDRO J. URTREGER; LAURA B. TODARO

Cdad Autonoma de Buenos Aires

Congreso; Segunda Reunión Conjunta de Sociedades de BioCiencias; 2017

Sociedad Argentina de Investigación Clínica (SAIC)

Cancer stem cells (CSC) are resistant to chemotherapy and radiation and they are also considered as metastasis seed.In order to suggest CSCs as a new therapeutic-intervention target, in this work we propose to study the effect of retinoid ATRA and HER2 inhibitor Lapatinib treatments on:A) Expression profile of pluripotent genes, retinoid receptors system and E-Caherin levels.B) In vitro invasive capacity and in vivo metastatic potential.For this purpose, the triple negative murine cell line 4T1 (tumorigenic and metastatic in BALB/c mice and expressing HER2 in its CSC component) was used.Through RT-qPCR, we could observe that ATRA (1uM) and Lapatinib (1uM) treatments, separately or in combination, were able to increase both RARa and RARg expression and decrease RARb receptor levels. Moreover, the same treatments induced an increment in E-Cadherin and reduced the expression of the main pluripotential genes: Nanog, OCT4 and SOX2. Regarding parameters associated with malignant progression using Matrigel-coated transwells, we observed that ATRA treatment increased CSC invasive capacity, however in experimental metastases assays with pretreated-CSC, this retinoid significantly decreases lung colonization. The treatments with both ATRA and Lapatinib were able to induce CSC differentiation and reduced their lung nesting ability, leading to a less malignant phenotype.