title: A physical sciences network characterization of circulating tumor cell aggregate transport.
abstract: Circulating tumor cells (CTC) have been implicated in the hematogenous spread of cancer. To investigate the fluid phase of cancer from a physical sciences perspective, the multi-institutional Physical Sciences-Oncology Center (PS-OC) Network performed multidisciplinary biophysical studies of single CTC and CTC aggregates from a patient with breast cancer. CTCs, ranging from single cells to aggregates comprised of 2-5 cells, were isolated using the high-definition CTC assay and biophysically profiled using quantitative phase microscopy. Single CTCs and aggregates were then modeled in an in vitro system comprised of multiple breast cancer cell lines and microfluidic devices used to model E-selectin mediated rolling in the vasculature. Using a numerical model coupling elastic collisions between red blood cells and CTCs, the dependence of CTC vascular margination on single CTCs and CTC aggregate morphology and stiffness was interrogated. These results provide a multifaceted characterization of single CTC and CTC aggregate dynamics in the vasculature and illustrate a framework to integrate clinical, biophysical, and mathematical approaches to enhance our understanding of the fluid phase of cancer.
authors: Department of Biomedical Engineering, Cornell University, Ithaca, New York;
authors: Michael R
authors: MR
authors: King
authors: Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, Oregon;
authors: Kevin G
authors: KG
authors: Phillips
authors: Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, Oregon; Divison of Hematology and Medical Oncology, School of Medicine, Oregon Health and Science University, Portland, Oregon; and.
authors: Annachiara
authors: A
authors: Mitrugno
authors: Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, Texas;
authors: Tae-Rin
authors: TR
authors: Lee
authors: Department of Biomedical Engineering, Cornell University, Ithaca, New York;
authors: Adelaide M E
authors: AM
authors: de Guillebon
authors: Department of Biomedical Engineering, Cornell University, Ithaca, New York;
authors: Siddarth
authors: S
authors: Chandrasekaran
authors: Department of Biomedical Engineering, Cornell University, Ithaca, New York;
authors: Matthew J
authors: MJ
authors: McGuire
authors: Department of Chemical Engineering, University of New Hampshire, Durham, New Hampshire.
authors: Russell T
authors: RT
authors: Carr
authors: Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, Oregon;
authors: Sandra M
authors: SM
authors: Baker-Groberg
authors: Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, Oregon;
authors: Rachel A
authors: RA
authors: Rigg
authors: Department of Biological Sciences, University of Southern California, Los Angeles, California;
authors: Anand
authors: A
authors: Kolatkar
authors: Department of Biological Sciences, University of Southern California, Los Angeles, California;
authors: Madelyn
authors: M
authors: Luttgen
authors: Scripps Clinic Medical Group, Scripps Clinic, La Jolla, California;
authors: Kelly
authors: K
authors: Bethel
authors: Department of Biological Sciences, University of Southern California, Los Angeles, California;
authors: Peter
authors: P
authors: Kuhn
authors: Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, Texas;
authors: Paolo
authors: P
authors: Decuzzi
authors: Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, Oregon; Divison of Hematology and Medical Oncology, School of Medicine, Oregon Health and Science University, Portland, Oregon; and mccartyo@ohsu.edu.
authors: Owen J T
authors: OJ
authors: McCarty
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002465:Cell Movement; D019040:E-Selectin / Q000378:metabolism*; D005260:Female; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D057900:Transcytosis / Q000502:physiology*
chemical_list: D019040:E-Selectin
keywords: breast cancer; cell lines; circulating tumor cell; fluid dynamics; hemodynamics; immersed finite element method; metastasis; microfluidics; physics of cancer; quantitative phase microscopy