title: Evolution of cellular morpho-phenotypes in cancer metastasis.
abstract: Intratumoral heterogeneity greatly complicates the study of molecular mechanisms driving cancer progression and our ability to predict patient outcomes. Here we have developed an automated high-throughput cell-imaging platform (htCIP) that allows us to extract high-content information about individual cells, including cell morphology, molecular content and local cell density at single-cell resolution. We further develop a comprehensive visually-aided morpho-phenotyping recognition (VAMPIRE) tool to analyze irregular cellular and nuclear shapes in both 2D and 3D microenvironments. VAMPIRE analysis of ~39,000 cells from 13 previously sequenced patient-derived pancreatic cancer samples indicate that metastasized cells present significantly lower heterogeneity than primary tumor cells. We found the same morphological signature for metastasis for a cohort of 10 breast cancer cell lines. We further decipher the relative contributions to heterogeneity from cell cycle, cell-cell contact, cell stochasticity and heritable morphological variations.
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Wu
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Jude M
authors.initials: JM
authors.lastname: Phillip
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Shyam B
authors.initials: SB
authors.lastname: Khatau
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Wei-Chiang
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stirman
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rosseel
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Tschudi
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Van Patten
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wong
authors.affiliation: Department of Pathology, UT MD Anderson Cancer Center, Houston, Texas, 77030, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Baras
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Leek
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.|Department of Pathology and the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000473:pathology; D002452:Cell Count; D045744:Cell Line, Tumor; D048430:Cell Shape; D019295:Computational Biology / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology; D015203:Reproducibility of Results; D059010:Single-Cell Analysis / Q000379:methods*; D059016:Tumor Microenvironment; D055815:Young Adult