Rapidly quantifying drug sensitivity of dispersed and clumped breast cancer cells by mass profiling.
Live cell mass profiling is a promising new approach for rapidly quantifying responses to therapeutic agents through picogram-scale changes in cell mass over time. A significant barrier in mass profiling is the inability of existing methods to handle pleomorphic cellular clusters and clumps, which are more commonly present in patient-derived samples or tissue cultures than are isolated single cells. Here we demonstrate automated Live Cell Interferometry (LCI) as a rapid and accurate quantifier of the sensitivity of single cell and colony-forming human breast cancer cell lines to the HER2-directed monoclonal antibody, trastuzumab (Herceptin). The relative sensitivities of small samples (<500 cells) of four breast cancer cell lines were determined tens-to-hundreds of times faster than is possible with traditional proliferation assays. These LCI advances in clustered sample assessment and speed open up the possibility for therapeutic response testing of patient-derived solid tumor samples, which are viable only for short periods ex vivo and likely to be in the form of cell aggregates and clusters.
Bioengineering Interdepartmental Program, Los Angeles, California, USA.
Jennifer
J
Chun
Thomas A
TA
Zangle
Theodora
T
Kolarova
Richard S
RS
Finn
Michael A
MA
Teitell
Jason
J
Reed
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007368:Interferometry / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human