Evolution of cellular morpho-phenotypes in cancer metastasis.
Evolution of cellular morpho-phenotypes in cancer metastasis.
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DOI：
10.1038/srep18437
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发表时间：
2015-12-17
影响因子：
4.6
通讯作者：
Wirtz D
中科院分区：
文献类型：
--
作者：
Wu PH;Phillip JM;Khatau SB;Chen WC;Stirman J;Rosseel S;Tschudi K;Van Patten J;Wong M;Gupta S;Baras AS;Leek JT;Maitra A;Wirtz D
肿瘤内异质性极大地复杂化了驱动癌症进展的分子机制的研究和我们预测患者预后的能力。在这里，我们开发了一个自动化的高通量细胞成像平台（htCIP），使我们能够以单细胞分辨率提取有关单个细胞的高含量信息，包括细胞形态，分子含量和局部细胞密度。我们进一步开发了一个全面的视觉辅助形态表型识别（VAMPIRE）工具来分析二维和三维微环境中的不规则细胞和核形状。对13例先前测序的患者来源的胰腺癌样本中约39,000个细胞的VAMPIRE分析表明，转移细胞的异质性明显低于原发肿瘤细胞。我们在10个乳腺癌细胞系的队列中发现了相同的转移形态学特征。我们进一步解释了细胞周期、细胞间接触、细胞随机性和可遗传形态变异对异质性的相对贡献。
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.