Figure 9

Molecular profile of breast cancer cells defines trastuzumab efficiency. (A) SKBR3 cells have the highest levels of HER2, Syn-1, HPSE1 and HS on the cell surface and low levels of HS shed to the medium. This cell is the most sensitive to trastuzumab in cell viability assays. Since HS and trastuzumab interact, as proved by FRET, HS enhances the amounts of trastuzumab available on the cell surface to interact with HER2, facilitating the blocking of this receptor by the antibody. (B), MCF7 cells present intermediate levels of HER2 and Syn-1, low levels of HPSE1 expression and similar levels of HS on the cell surface and shed to the medium, decreasing their viability in the presence of trastuzumab with higher doses. (C), MCF7 cells transfected with HPSE1 cDNA present the lowest levels of HER2 and Syn-1 and high levels of HPSE1. The cell surface HS decreases and the shedding of this molecule increases significantly in these cells. High levels of HPSE1 leads to HS shedding that could capture trastuzumab in the medium, due to the affinity between HS and trastuzumab previously shown. Trastuzumab captured in the media prevents HER2 blocking, contributing to cellular resistance to trastuzumab.