Evolution of cellular morpho-phenotypes in cancer metastasis
Citations Over TimeTop 10% of 2015 papers
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.
Related Papers
- → Associated costs and benefits of a defended phenotype across multiple environments(2010)15 cited
- → In-silico identification of phenotype-biased functional modules(2012)14 cited
- [Characteristics of chronic obstructive pulmonary disease phenotypes based on high-resolution CT and the relationship with interleukin-6].(2010)
- [Alpha-1-antitrypsin deficiency. Phenotype study of 60 members of the same family].(1977)
- → Correlations of Malignancy in Cultured Cells(1988)