期刊
CELL
卷 178, 期 1, 页码 160-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.05.012
关键词
-
资金
- American-Italian Cancer Foundation Post-Doctoral Research Fellowship
- Hirshberg Foundation seed grant
- Tosteson and Fund for Medical Discovery Fellowship
- Burroughs Wellcome Fund
- NSF [PHY-1549535]
- SU2C
- Lustgarten Foundation
- V Foundation
- Affymetrix, Inc.
- NIH [T32GM007753, U01 CA215798, 2R01CA129933, 2U01EB012493, U01CA214297]
- Warshaw Institute for Pancreatic Cancer Research
- Verville Family Pancreatic Cancer Research Fund
- ESSCO Breast Cancer Research
- Breast Cancer Research Foundation
- Howard Hughes Medical Institute
- National Foundation for Cancer Research
- NCI [U01CA215798]
Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenchymal transition (EMT) and proliferative (PRO) phenotypes linked with mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling. Using high-content digital imaging of RNA in situ hybridization in 195 PDAC tumors, we quantified these EMT and PRO subpopulations in 319,626 individual cancer cells that can be classified within the context of distinct tumor gland units. Tumor gland typing provided an additional layer of intratumoral heterogeneity that was associated with differences in stromal abundance and clinical outcomes. This demonstrates the impact of the stroma in shaping tumor architecture by altering inherent patterns of tumor glands in human PDAC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据