HEME OXYGENASE-1 DECREASES THE INVASIVE FENOTYPE IN BREAST CANCER

CURINO, A.C.; FERRONATO, M.J.; ALONSO, E.N.; FERMENTO, M.E.; OBIOL, D.J.; FACCHINETTI, M.M.; GANDINI, N.A.

San Carlos de Bariloche

Congreso; Sistam 2015; 2015

CONICET

Cell invasioninvolves changes in cell-cell and cell-extracellular matrix interactions. TheE-cadherin (E-cadh) and β-catenin (β-cat) participate as anchor proteins ofepithelial cell-cell and have been deregulated in breast cancer (BC). Previousresults from our laboratory demonstrated the role of heme oxygenase 1 (HO-1) inthe progression of BC. The aim of this work was to study the role of HO-1 inthe modulation of these proteins and the regulation of cell migration andinvasion. In human BC biopsies, we detected by immunohistochemistry (IHC), thatthere is a positive correlation between the expression of HO-1 and E-cadh (p =0.0144; Spearman test). In the murine LM3 BC cells we observed byimmunofluorescence and western blot (WB) increased expression of E-cadh and β-cat(p <0.05, Chi square) after treatment with hemin (pharmacological activationof HO-1). These results were confirmed by stable overexpression of HO-1 in humanT47D BC cells. Also, we noted that pharmacological modulation of HO-1 withhemin in LM3 decreased in cell migration (wound healing test; p = 0.003, ANOVA)and cell invasion (matrigel assays; p = 0.0001, test Student). In addition,after treatment with hemin in these cells we noted decreased amount of stressfibers. In accordance with these results, we detected in LM3 cells MMP9 decreasedexpression by WB after pharmacological modulation. In a murine model ofsyngeneic cell transplantation by IHC we demonstrated that treating animalswith hemin is associated with increased expression of E-cadh (IRS IRS = 6 vscontrol = 3.5; p = 0.026, Mann Whitney test) and β-cat (IRS IRS = 5.15 vscontrol = 3.8; p = 0.028, Mann Whitney test). Moreover, we observed a decreasedin the count of new blood vessels after pharmacological modulation (p<0.05Chi square). In conclusion, these results indicate that HO-1 may counteract theinvasive phenotype in breast cancer.