Breast cancer-derived microparticles reduce cancer cell adhesion, an effect augmented by chemotherapy

Tumor-derived microparticles (TMPs), TMP, have been shown to support metastasis, in part by help
forming the pre-metastatic niche. We and others have demonstrated that chemotherapy contributes to
tumor cell aggressiveness via different mechanisms including TMP. However, the contribution of TMPs
to cell adhesion properties as part of the metastatic cascade has not been fully demonstrated. Here we
show that TMPs from highly metastatic cells or cells exposed to chemotherapy substantially reduce cell
adhesion and disrupt actin filament structure therefore altering their biomechanical forces further
implicating tumor cell dissemination as part of the metastatic cascade. These pro-metastatic effects are
mediated in part by CD44 highly expressed in TMPs obtained from metastatic cells or cells exposed to
chemotherapy when compared to cells with low metastatic potential. Consequently, pharmacological or
genetic ablation of CD44 expressed by TMPs increases tumor cell adhesion and re-organizes actin filament
structure. Increased CD44 expression in TMPs was also demonstrated in breast cancer patients after they
were treated with paclitaxel chemotherapy. Overall, our study provides further insight into the role of
TMPs in promoting metastasis, an effect which is augmented in response to chemotherapy.