Circulating tumor cells (CTCs) are rare cells and the presence of these cells may indicate a poor prognosis and a high potential for metastasis. Despite highly promising clinical applications, CTCs have not been investigated thoroughly, due to many technical limitations faced in their isolation and identification. Current CTC detection techniques mostly take the epithelial marker epithelial cell adhesion molecule (EpCAM), however, accumulating evidence suggests that CTCs show heterogeneous EpCAM expression due to the epithelial-to-mesenchymal transition (EMT). In this study, we report that a microchip filter device incorporating slit arrays and 3-dimensional flow that can separate heterogeneous population of cells with marker for CTCs. To select target we cultured breast cancer cells under prolonged mammosphere culture conditions which induced EMT phenotype. Under these conditions, cells show upregulation of caveolin1 (CAV1) but down-regulation of EpCAM expression. The proposed device which contains CAV1-EpCAM conjugated bead has several tens of times increased throughput. More importantly, this platform enables the enhanced capture yield from metastatic breast cancer patients and obtained cells that expressed various EMT markers. Further understanding of these EMT-related phenotypes will lead to improved detection techniques and may provide an opportunity to develop therapeutic strategies for effective treatment and prevention of cancer metastasis.
|Number of pages||10|
|Publication status||Published - 2014 Aug|
Bibliographical noteFunding Information:
We would like to acknowledge Dr. Donghyun Park, Dr. Chang Eun Yoo, Dr. Hun Joo Lee, Jin-Mi Oh, Sanghyun Baek, and Dr. Kyung Yeon Han for helpful discussion and technical assistance. This work was supported by National Research Foundation of Korea (NRF)> grant funded by the Korea government to Y.-S, K. (No. 2011-0030043 and 2012R1A1A2008713 ).
- 3D-flow path membrane filter
ASJC Scopus subject areas
- Mechanics of Materials
- Ceramics and Composites