Abstract 5161: Cell mechanics-cytoskeleton-membrane protein transduction loop mediates brain metastasis of breast cancer cells

Abstract

Abstract Brain metastasis is the worst stage of breast cancer, as no therapy exists that prevents or eliminates breast cancer spreading to the brain. New therapeutic strategies depend on specific knowledge of tumor cell properties that allow breast cancer cells get through blood-brain barrier and grow in brain tissue. To provide information in this direction, we developed a microfluidic single-cell patch clamp microdevice to study the electrophysiological and biomechanical properties of human breast cancer brain metastatic cells for the first time. The results show that the brain metastatic cells possess higher membrane resistance and greater membrane stiffness compared to non-brain metastatic cells. The over-expression of HER2 and EGFR decrease the cell membrane resistance, while increase the cell stiffness, which correlates with the enhanced cell invasion through the in vitro blood-brain barrier and increased formation of brain metastatic loci in the xenograft mice. Gene expression analysis of the brain metastatic cells identifies cell membrane protein PCDH7 mediates the increased cell mechanics property functionally, and PCDH7 is also an enhancer of blood-brain barrier crossing and brain colonization for the brain metastatic cells, through the cytoskeleton rearrangement mechanism. This cell mechanics-cytoskeleton-PCDH7 protein loop mechanism may prove to be an attraction therapeutic target to block the brain metastasis of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5161. doi:10.1158/1538-7445.AM2011-5161