文章基本信息

标题：Evolution of cellular morpho-phenotypes in cancer metastasis
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作者：Pei-Hsun Wu ; Jude M. Phillip ; Shyam B. Khatau 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：5
期号：1
DOI：10.1038/srep18437
语种：English
出版社：Springer Nature
摘要：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.