Evolution of cellular morpho-phenotypes in cancer metastasis

Pei Hsun Wu, Jude M. Phillip, Shyam B. Khatau, Wei Chiang Chen, Jeffrey Stirman, Sophie Rosseel, Katherine Tschudi, Joshua Van Patten, Michael Wong, Sonal Gupta, Alexander S. Baras, Jeffrey T. Leek, Anirban Maitra, Denis Wirtz

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number18437
JournalScientific reports
Volume5
DOIs
StatePublished - Dec 17 2015

ASJC Scopus subject areas

  • General

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