PMID- 31947893 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 12 IP - 1 DP - 2020 Jan 3 TI - High-Throughput Label-Free Isolation of Heterogeneous Circulating Tumor Cells and CTC Clusters from Non-Small-Cell Lung Cancer Patients. LID - 10.3390/cancers12010127 [doi] LID - 127 AB - (1) Background: Circulating tumor cell (CTC) clusters are emerging as clinically significant harbingers of metastases in solid organ cancers. Prior to engaging these CTC clusters in animal models of metastases, it is imperative for technology to identify them with high sensitivity. These clusters often present heterogeneous surface markers and current methods for isolation of clusters may fall short. (2) Methods: We applied an inertial microfluidic Labyrinth device for high-throughput, biomarker-independent, size-based isolation of CTCs/CTC clusters from patients with metastatic non-small-cell lung cancer (NSCLC). (3) Results: Using Labyrinth, CTCs (PanCK+/DAPI+/CD45-) were isolated from patients (n = 25). Heterogeneous CTC populations, including CTCs expressing epithelial (EpCAM), mesenchymal (Vimentin) or both markers were detected. CTCs were isolated from 100% of patients (417 +/- 1023 CTCs/mL). EpCAM- CTCs were significantly greater than EpCAM+ CTCs. Cell clusters of >/=2 CTCs were observed in 96% of patients-of which, 75% were EpCAM-. CTCs revealed identical genetic aberrations as the primary tumor for RET, ROS1, and ALK genes using fluorescence in situ hybridization (FISH) analysis. (4) Conclusions: The Labyrinth device recovered heterogeneous CTCs in 100% and CTC clusters in 96% of patients with metastatic NSCLC. The majority of recovered CTCs/clusters were EpCAM-, suggesting that these would have been missed using traditional antibody-based capture methods. FAU - Zeinali, Mina AU - Zeinali M AD - Chemical Engineering, University of Michigan, 2800 Plymouth Road, NCRC, Building 20-3rd Floor, Ann Arbor, MI 48109, USA. AD - Biointerfaces Institute, University of Michigan, 2800 Plymouth Road, NCRC B10-A184, Ann Arbor, MI 48109, USA. AD - Institute for Medical Technology of Heidelberg University & University of Applied Sciences Mannheim, Paul-Wittsack-Strasse 10, 68163 Mannheim, Germany. FAU - Lee, Maggie AU - Lee M AD - Chemical Engineering, University of Michigan, 2800 Plymouth Road, NCRC, Building 20-3rd Floor, Ann Arbor, MI 48109, USA. AD - Biointerfaces Institute, University of Michigan, 2800 Plymouth Road, NCRC B10-A184, Ann Arbor, MI 48109, USA. FAU - Nadhan, Arthi AU - Nadhan A AD - Chemical Engineering, University of Michigan, 2800 Plymouth Road, NCRC, Building 20-3rd Floor, Ann Arbor, MI 48109, USA. AD - Biointerfaces Institute, University of Michigan, 2800 Plymouth Road, NCRC B10-A184, Ann Arbor, MI 48109, USA. FAU - Mathur, Anvya AU - Mathur A AD - Chemical Engineering, University of Michigan, 2800 Plymouth Road, NCRC, Building 20-3rd Floor, Ann Arbor, MI 48109, USA. AD - Biointerfaces Institute, University of Michigan, 2800 Plymouth Road, NCRC B10-A184, Ann Arbor, MI 48109, USA. FAU - Hedman, Casey AU - Hedman C AD - Molecular, Cellular, and Developmental Biology, University of Michigan, 1105 North University Avenue, 2220 Biological Science Building, Ann Arbor, MI 48109, USA. FAU - Lin, Eric AU - Lin E AUID- ORCID: 0000-0001-7571-1657 AD - Chemical Engineering, University of Michigan, 2800 Plymouth Road, NCRC, Building 20-3rd Floor, Ann Arbor, MI 48109, USA. AD - Biointerfaces Institute, University of Michigan, 2800 Plymouth Road, NCRC B10-A184, Ann Arbor, MI 48109, USA. FAU - Harouaka, Ramdane AU - Harouaka R AD - Department of Internal Medicine, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA. FAU - Wicha, Max S AU - Wicha MS AD - Department of Internal Medicine, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA. FAU - Zhao, Lili AU - Zhao L AD - Biostatistics Department, University of Michigan, Ann Arbor, MI 48109, USA. FAU - Palanisamy, Nallasivam AU - Palanisamy N AUID- ORCID: 0000-0002-0633-9772 AD - Department of Urology, Henry Ford Health System, 1 Ford Place, Room 2D26, Detroit, MI 48202, USA. FAU - Hafner, Mathias AU - Hafner M AD - Institute for Medical Technology of Heidelberg University & University of Applied Sciences Mannheim, Paul-Wittsack-Strasse 10, 68163 Mannheim, Germany. FAU - Reddy, Rishindra AU - Reddy R AUID- ORCID: 0000-0002-4337-5051 AD - Department of Surgery, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA. FAU - Kalemkerian, Gregory P AU - Kalemkerian GP AD - Department of Internal Medicine, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA. FAU - Schneider, Bryan J AU - Schneider BJ AD - Department of Internal Medicine, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA. FAU - Hassan, Khaled A AU - Hassan KA AD - Department of Internal Medicine, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA. FAU - Ramnath, Nithya AU - Ramnath N AD - Department of Internal Medicine, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA. AD - Veterans Administration Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA. FAU - Nagrath, Sunitha AU - Nagrath S AD - Chemical Engineering, University of Michigan, 2800 Plymouth Road, NCRC, Building 20-3rd Floor, Ann Arbor, MI 48109, USA. AD - Biointerfaces Institute, University of Michigan, 2800 Plymouth Road, NCRC B10-A184, Ann Arbor, MI 48109, USA. LA - eng GR - R01 CA208335/CA/NCI NIH HHS/United States GR - R33 CA202867/CA/NCI NIH HHS/United States GR - 1-R01-CA-208335-01-A1/NH/NIH HHS/United States GR - 5-R33-CA-202867-02/NH/NIH HHS/United States PT - Journal Article DEP - 20200103 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC7016759 OTO - NOTNLM OT - CTC clusters OT - circulating tumor cells (CTCs) OT - epithelial-to-mesenchymal transition (EMT) OT - inertial microfluidics OT - non-small-cell lung cancer (NSCLC) COIS- The authors declare no conflict of interest. EDAT- 2020/01/18 06:00 MHDA- 2020/01/18 06:01 PMCR- 2020/01/03 CRDT- 2020/01/18 06:00 PHST- 2019/11/13 00:00 [received] PHST- 2019/12/17 00:00 [revised] PHST- 2019/12/30 00:00 [accepted] PHST- 2020/01/18 06:00 [entrez] PHST- 2020/01/18 06:00 [pubmed] PHST- 2020/01/18 06:01 [medline] PHST- 2020/01/03 00:00 [pmc-release] AID - cancers12010127 [pii] AID - cancers-12-00127 [pii] AID - 10.3390/cancers12010127 [doi] PST - epublish SO - Cancers (Basel). 2020 Jan 3;12(1):127. doi: 10.3390/cancers12010127.