title: Predicting therapy response in live tumor cells isolated with the flexible micro spring array device.
abstract: Cells disseminated from primary epithelial tumors into peripheral blood, called circulating tumor cells (CTCs), can be monitored to assess metastases and to provide a surrogate marker of treatment response. Here, we demonstrate how the flexible micro spring array (FMSA) device-a novel microfluidic device that enriches CTCs by two physical parameters: size and deformability-could be used in the rational development of treatment intervention and as a method to study the fundamental biology of CTCs. Cancer cells of different origins were spiked into healthy samples of donor blood to mimic blood samples of metastatic cancer patients. This spiked human blood was filtered using the FMSA device, and the recovered cells were successfully expanded in vitro and in a novel in vivo system. A series of experiments were performed to characterize these cells and to investigate the effect of chemotherapy on the resulting cultures. As few as 20 colon cancer cells in 7.5 mL blood could be isolated with the FMSA device, expanded both in vitro and in vivo and used at 25 cells per well to obtain significant and reliable chemosensitivity data. We also show that isolating a low number of viable patient CTCs and maintaining them in culture for a few weeks is possible. The isolation of viable cancer cells from human blood using the FMSA device provides a novel and realistic means for studying the biology of viable CTCs and for testing drug efficacy on these rare cells-a hypothesis that can be tested in future clinical trials.
authors.affiliation: Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Division of Hematology-Oncology, Penn State Hershey Cancer Institute; Hershey, PA, USA.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Gallant
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Matthew
authors.forename: Hairong
authors.initials: H
authors.lastname: Cheng
authors.forename: Ramdane
authors.initials: R
authors.lastname: Harouaka
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Lamparella
authors.forename: Miriam
authors.initials: M
authors.lastname: Kunkel
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Yang
authors.forename: Harold A
authors.initials: HA
authors.lastname: Harvey
authors.forename: Leah V
authors.initials: LV
authors.lastname: Cream
authors.forename: Suresh M
authors.initials: SM
authors.lastname: Kumar
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Robertson
authors.forename: Siyang
authors.initials: S
authors.lastname: Zheng
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Drabick
authors.forename: Cristina I
authors.initials: CI
authors.lastname: Truica
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D000970:Antineoplastic Agents / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D045325:HCT116 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D016513:Mice, SCID; D046210:Microfluidic Analytical Techniques; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D019736:Prostheses and Implants; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin
keywords: circulating tumor cells; drug sensitivity testing; microfluidic; personalized medicine; viable cell capture