| Literature DB >> 31155233 |
Matteo Ligorio1, Srinjoy Sil2, Jose Malagon-Lopez3, Linda T Nieman2, Sandra Misale2, Mauro Di Pilato4, Richard Y Ebright2, Murat N Karabacak5, Anupriya S Kulkarni2, Ann Liu2, Nicole Vincent Jordan2, Joseph W Franses2, Julia Philipp2, Johannes Kreuzer2, Niyati Desai2, Kshitij S Arora6, Mihir Rajurkar2, Elad Horwitz2, Azfar Neyaz2, Eric Tai2, Neelima K C Magnus2, Kevin D Vo2, Chittampalli N Yashaswini2, Francesco Marangoni4, Myriam Boukhali2, Jackson P Fatherree2, Leah J Damon2, Kristina Xega2, Rushil Desai2, Melissa Choz2, Francesca Bersani2, Adam Langenbucher2, Vishal Thapar3, Robert Morris2, Ulrich F Wellner7, Oliver Schilling8, Michael S Lawrence2, Andrew S Liss9, Miguel N Rivera3, Vikram Deshpande3, Cyril H Benes2, Shyamala Maheswaran1, Daniel A Haber10, Carlos Fernandez-Del-Castillo1, Cristina R Ferrone1, Wilhelm Haas2, Martin J Aryee11, David T Ting12.
Abstract
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.Entities:
Keywords: mass spectrometry; pancreatic cancer; pancreatic ductal adenocarcinoma; single cell RNA-sequencing; single cell spatial analysis; stromal microenvironment; tumor architecture
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Year: 2019 PMID： 31155233 PMCID： PMC6697165 DOI： 10.1016/j.cell.2019.05.012
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582