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

doi:10.1038/srep18437

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 journal › Article › peer-review

34 Scopus citations

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 language	English (US)
Article number	18437
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep18437
State	Published - Dec 17 2015

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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.",

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

note = "Funding Information: The authors acknowledge funding from the National Cancer Institute (U54CA143868) and American Heart Association (12POST12050638). We thank Prof. Y. Tseng for critical discussions and reading of the manuscript.",

year = "2015",

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day = "17",

doi = "10.1038/srep18437",

language = "English (US)",

volume = "5",

journal = "Scientific reports",

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AU - Wu, Pei Hsun

AU - Phillip, Jude M.

AU - Khatau, Shyam B.

AU - Chen, Wei Chiang

AU - Stirman, Jeffrey

AU - Rosseel, Sophie

AU - Tschudi, Katherine

AU - Van Patten, Joshua

AU - Wong, Michael

AU - Gupta, Sonal

AU - Baras, Alexander S.

AU - Leek, Jeffrey T.

AU - Maitra, Anirban

AU - Wirtz, Denis

N1 - Funding Information: The authors acknowledge funding from the National Cancer Institute (U54CA143868) and American Heart Association (12POST12050638). We thank Prof. Y. Tseng for critical discussions and reading of the manuscript.

PY - 2015/12/17

Y1 - 2015/12/17

N2 - 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.

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Evolution of cellular morpho-phenotypes in cancer metastasis

Abstract

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