Much effort has gone into developing fluid biopsies of patient peripheral blood for the monitoring of metastatic cancers. One common approach is to isolate and analyze tumor cells in the peripheral blood. Widespread clinical implementation of this approach has been hindered by the current choice of targeting epithelial markers known to be highly variable in primary tumor sites. Here, we review current antigen-based tumor cell isolation strategies and offer biological context for commonly studied cancer surface markers. Expression levels of the most common markers are quantitated for three breast cancer and two non-small cell lung cancer (NSCLC) lineage models. These levels are contrasted with that present on healthy peripheral blood mononuclear cells (PBMC) for comparison to expected background levels in a fluid biopsy setting. A key feature of this work is establishing a metric of markers per square micrometer. This describes an average marker density on the cell membrane surface, which is a critical metric for emerging isolation strategies. These results serve to extend expression of key tumor markers in a sensitive and dynamic manner beyond traditional positive/negative immunohistochemical staining to guide future fluid biopsy targeting strategies.
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The authors acknowledge partial financial support from a National Science Foundation Career Award grant awarded to BJB (NS F-1351531) and a National Cancer Institute Cancer Nanotechnology Traineeship (NCI-CNT C) awarded to JLL through grant R25CA153954. The authors confirm that the funders had no influence over the study design, content of the article, or selection of this journal.
Cahall, Calvin F.; Lilly, Jacob L.; Hirschowitz, Edward A.; and Berron, Brad J., "A Quantitative Perspective on Surface Marker Selection for the Isolation of Functional Tumor Cells" (2015). Chemical and Materials Engineering Faculty Publications. 13.