Multivalent Binding, Cell Rolling, and Micropatterning for Enhanced Detection of Circulating Tumor Cells
thesisposted on 22.02.2013, 00:00 by Ja Hye Myung
In order to distinguish essays and pre-prints from academic theses, we have a separate category. These are often much longer text based documents than a paper.
Circulating tumor cells (CTCs) in the blood of cancer patients are related to cancer progress and metastasis. CTCs can be isolated from non-epithelial, hematological cells using one of antibodies against epithelial cell surface markers called epithelial-cell-adhesion-molecule (EpCAM), human-epidermal-growth-factor- receptor-2 (HER-2), and prostate-specific-antigen (PSA). However, the effective detection of CTCs has a challenge coming from the extreme rarity of CTCs (approximately one tumor cell in the background of one million - one billion blood cells). Recently, we have developed a novel surface system that is programmed to mimic two naturally occurring processes to detect these rare cells at great sensitivity and selectivity: i) E-selectin- mediated cancer cell rolling and ii) the multivalent binding through multiple antibodies immobilized on a dendrimer. A poly(amidoamine) dendrimer, a spherical polymer with multiple reactive groups on its surface, was used to mediate the multivalent binding effect. The biomimetic combination of E-selectin and antibody- dendrimer conjugate was micropatterned on a multifunctional surface using a gasket for effective recruitment and specific isolation of tumor cells, respectively. With in vitro spiked cancer cells in culture media or human blood, the multifunctional surfaces resulted in a significantly enhanced tumor cell detection by ~39-fold at maximum with higher binding stability than the control surfaces. This study demonstrates a novel surface engineering approach to exploiting the E-selectin-mediated cell rolling and strong multivalent binding, which has great potential for clinically significant detection of CTCs.