Bulletin of the American Physical Society
2009 APS March Meeting
Volume 54, Number 1
Monday–Friday, March 16–20, 2009; Pittsburgh, Pennsylvania
Session W3: Physics of Circulating Tumor Cells and Metastasis |
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Sponsoring Units: DBP Chair: Jerry Lee, National Cancer Institute Room: 301/302 |
Thursday, March 19, 2009 11:15AM - 11:51AM |
W3.00001: Single-molecule Force Spectroscopy of Intercellular Adhesion in Cancer Invited Speaker: The progression of several human cancers correlates with the loss of a-catenin from E-cadherin-rich intercellular junctions and loss of adhesion. However, the potential role of a-catenin in directly modulating the adhesive function of individual E-cadherin molecules in human cancer is unknown. Here we use single-molecule force spectroscopy to probe the tensile strength, lifetime, and interaction energy between live human parental breast cancer cells lacking a-catenin and these cells where a-catenin is re-expressed. We find that the tensile strength and lifetime of single E-cadherin bonds between parental cells are significantly lower over a wide range of loading rates. Statistical analysis of the force-displacement spectra reveals that single cadherin bonds between cancer cells feature an exceedingly low energy barrier against tensile forces and low molecular rigidity. These results suggest that the loss of a-catenin drastically reduces the adhesive force between individual cadherin pairs on adjoining cells, explain the global loss of cell adhesion in human breast cancer cells and show that the forced expression of a-catenin in cancer cells can restore both higher intercellular avidity and intermolecular E-cadherin affinity. [Preview Abstract] |
Thursday, March 19, 2009 11:51AM - 12:27PM |
W3.00002: Studying Cell Motility and Cell Mechanics with ``Designer Cells" Invited Speaker: Micro/nanopatterning allows for the creation of cells of identical morphologies and with ``designed'' organization of the cytoskeleton. Analysis of such ``Designer Cells'' via high-resolution microscopy allows for studying the intracellular processes related to cytoskeletal dynamics and cancer invasiveness in quantitative detail. In addition, three-dimensional imaging can be used to reconstruct cell shapes and describe these shapes by mathematical functions - it is found that cells are constant-curvature surfaces corresponding to the minima of relatively simple energy functionals describing cell micromechanics. These and other results have implications for physical assays with which to diagnose the metastatic form of cancer. [Preview Abstract] |
Thursday, March 19, 2009 12:27PM - 1:03PM |
W3.00003: Nanostructured Substrates for Capturing Circulating Tumor Cells in Whole Blood Invited Speaker: Over the past decade, circulating tumor cells (CTCs) has become an emerging ``biomarker'' for detecting early-stage cancer metastasis, predicting patient prognosis, as well as monitoring disease progression and therapeutic outcomes. However, isolation of CTCs has been technically challenging due to the extremely low abundance (a few to hundreds per ml) of CTCs among a high number of hematologic cells (109 per mL) in the blood. Our joint research team at UCLA has developed a new cell capture technology for quantification of CTCs in whole blood samples. Similar to most of the existing approaches, epithelial cell adhesion molecule antibody (anti-EpCAM) was grafted onto the surfaces to distinguish CTCs from the surrounding hematologic cells. The uniqueness of our technology is the use of nanostructured surfaces, which facilitates local topographical interactions between CTCs and substrates at the very first cell/substrate contacting time point. We demonstrated the ability of these nanostructured substrates to capture CTCs in whole blood samples with significantly improved efficiency and selectivity. The successful demonstration of this cell capture technology using brain, breast and prostate cancer cell lines encouraged us to test this approach in clinical setting. We have been able to bond our first validation study with a commercialized technology based on the use of immunomagnetic nanoparticles. A group of clinically well-characterized prostate cancer patients at UCLA hospital have been recruited and tested in parallel by these two technologies. [Preview Abstract] |
Thursday, March 19, 2009 1:03PM - 1:39PM |
W3.00004: A portable circulating tumor cell capture microdevice Invited Speaker: Sensitive detection of earliest metastatic spread of tumors in a minimally invasive and user-friendly manner will revolutionize the clinical management of cancer patients. The current methodologies for circulating tumor cell (CTC) capture and identification have significant limitations including time, cost, limited capture efficiency and lack of standardization. We have developed and optimized a novel parylene membrane filter-based portable microdevice for size-based isolation of CTC from human peripheral blood. Following characterization with a model system to study the recovery rate and enrichment factor, a comparison of the microdevice with the commercially available system using blood from cancer patients demonstrated superior recovery rate and the promise of clinical utility of the microdevice. The development of the microdevice and its potential clinical applicability will be discussed. [Preview Abstract] |
Thursday, March 19, 2009 1:39PM - 2:15PM |
W3.00005: Detection and Characterization of Circulating Tumor Cells Invited Speaker: Circulating tumor cells (CTCs) occur in blood below the concentration of 1 cell in a hundred thousand white blood cells and can provide prognostic and diagnostic information about the underlying disease. While numeration of CTCs has provided useful information on progression-free and overall survival, it does not provide guidance of treatment choice. Since CTCs are presumed contain features of the metastatic tissue, characterization of cancer markers on these cells could help selection of treatment. At such low concentrations, reliable location and identification of these cells represents a significant technical challenge. Automated digital microscopy (ADM) provides high levels of sensitivity, but the analysis time is prohibitively long for a clinical assay. Enrichment methods have been developed to reduce sample size but can result in cell loss. A major barrier in reliable enrichment stems from the biological heterogeneity of CTCs, exhibited in a wide range of genetic, biochemical, immunological and biological characteristics. We have developed an approach that uses fiber-optic array scanning technology (FAST) to detect CTCs. Here, laser-printing optics are used to excite 300,000 cells/sec, and fluorescence from immuno-labels is collected in an array of optical fibers that forms a wide collection aperture. The FAST cytometer can locate CTCs at a rate that is 500 times faster than an ADM with comparable sensitivity and improved specificity. With this high scan rate, no enrichment of CTCs is required. The target can be a cytoplasm protein with a very high expression level, which reduces sensitivity to CTC heterogeneity. We use this method to measure expression levels of multiple markers on CTCs to help predict effective cancer treatment. [Preview Abstract] |
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