title: Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells.
abstract: Identification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all tumor cell types. We investigated whether the five subtypes of human breast cancer cells that have been defined by global gene expression profiling-normal-like, basal, HER2-positive, and luminal A and B-were identified by CellSearch, a US Food and Drug Administration-approved test that uses antibodies against the cell surface-expressed epithelial cell adhesion molecule (EpCAM) to isolate circulating tumor cells. We used global gene expression profiling to determine the subtypes of a well-defined panel of 34 human breast cancer cell lines (15 luminal, nine normal-like, five basal-like, and five Her2-positive). We mixed 50-150 cells from 10 of these cell lines with 7.5 mL of blood from a single healthy human donor, and the mixtures were subjected to the CellSearch test to isolate the breast cancer cells. We found that the CellSearch isolation method, which uses EpCAM on the surface of circulating tumor cells for cell isolation, did not recognize, in particular, normal-like breast cancer cells, which in general have aggressive features. New tests that include antibodies that specifically recognize normal-like breast tumor cells but not cells of hematopoietic origin are needed.
authors.affiliation: Department of Medical Oncology, Josephine Nefkens Institute, Cancer Genomics Centre, Rotterdam, the Netherlands. a.sieuwerts@erasmusmc.nl
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.forename: Jaco
authors.initials: J
authors.lastname: Kraan
authors.forename: Joan
authors.initials: J
authors.lastname: Bolt
authors.forename: Petra
authors.initials: P
authors.lastname: van der Spoel
authors.forename: Fons
authors.initials: F
authors.lastname: Elstrodt
authors.forename: Mieke
authors.initials: M
authors.lastname: Schutte
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Gratama
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
mesh_terms: D000912:Antibodies, Neoplasm / Q000097:blood*; D000951:Antigens, Neoplasm / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D011237:Predictive Value of Tests; D012107:Research Design
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule