Retinoids and HER2 inhibitors affect the behavior of mammary cancer stem cells

AGUSTINA TARUSELLI; DAMIAN E. BERARDI; ALEJANDRO J. URTREGER; LAURA B. TODARO

Cordoba

Congreso; LII Reunion Anual Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular; 2016

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

Cancer stem cells (CSC) are resistant to chemotherapy and radiation and are also considered as the metastasis seed. It was described that HER2 receptor would be involved in stem capacity maintenance. So, our objectives were: A) To assess the expression of HER2 receptor both in triple negative mammary cancer 4T1 cells and in its CSC derived population. B) To analyze the modulation of growth potential under retinoids (ATRA), Lapatinib (Lp, Her2 inhibitor) and the combined treatment. C) To evaluate soluble metaloprotease 9 (MMP9) activity on pre-treated CSC. Her2 was selectively expressed in the CSC population, in its active form. While ATRA had no effect, Lp caused a marked growth inhibition in 4T1 monolayers. When the same treatments were applied on CSC (soluble mammospheres culture), ATRA and Lp combination strongly inhibit the formation of these 3D structures, being them small and irregular, with high number of dead cells. Cells derived from pretreated mammospheres were seeded at low density in order to evaluate the clonogenic capacity. While ATRA and Lp reduced clonogenicity, the combined treatment induced a higher effect. Regarding MMP9 activity, the presence of ATRA increases this activity while no differences were found under Lp treatment. The results presented in this work could allow a new therapeutic approach for a subset of tumors lacking effective therapy till nowadays.