Evolution of cellular morpho-phenotypes in cancer metastasis

被引：72

作者：

Wu, Pei-Hsun ^{[1
,2
]}

Phillip, Jude M. ^{[1
,2
]}

Khatau, Shyam B. ^{[1
,2
]}

Chen, Wei-Chiang ^{[1
,2
]}

Stirman, Jeffrey ^{[1
]}

Rosseel, Sophie ^{[1
]}

Tschudi, Katherine ^{[1
]}

Van Patten, Joshua ^{[1
]}

Wong, Michael ^{[1
]}

Gupta, Sonal ^{[4
]}

Baras, Alexander S. ^{[3
]}

Leek, Jeffrey T. ^{[8
]}

Maitra, Anirban ^{[5
,6
,7
]}

Wirtz, Denis ^{[1
,2
,5
]}

机构：

[1] Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD 21218 USA

[2] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA

[4] UT MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[5] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA

[6] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA

[7] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA

[8] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

关键词：

LONG-TERM SURVIVAL; DUCTAL ADENOCARCINOMA; INTRATUMOR HETEROGENEITY; GENETIC-HETEROGENEITY; TUMOR-CELLS; MIGRATION; PANCREATICODUODENECTOMY; DIVERSITY; DYNAMICS; MARKERS;

D O I：

10.1038/srep18437

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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 similar to 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.

引用

页数：10

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