Binding of trastuzumab to ErbB2 is inhibited by a high pericellular density of hyaluronan.

ABSTRACT: Although trastuzumab is an efficient drug, primary and acquired resistance is a challenging problem. The authors have previously shown in mouse xenograft experiments that masking ErbB2 by hyaluronan leads to diminished binding of the antibody and consequent resistance. In the current work, they correlated trastuzumab binding with the pericellular density of hyaluronan in ErbB2-overexpressing human breast cancer samples. A method for quantifying the relative binding of trastuzumab was developed involving constant and low-frequency background subtraction, segmenting the image to membrane and background pixels followed by evaluation of trastuzumab fluorescence, normalized with the expression level of ErbB2, only in the membrane. The normalized binding of trastuzumab showed a negative correlat

SUBMITTER: Varadi T 

PROVIDER: S-EPMC3460360 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature