Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer

Autor: Murat Karabacak, Leah J. Damon, Andrew S. Liss, Jackson P. Fatherree, Richard Y. Ebright, Rushil Desai, Robert Morris, Daniel A. Haber, Mauro Di Pilato, Francesca Bersani, Jose Malagon-Lopez, Anupriya S. Kulkarni, Eric Tai, Nicole Vincent Jordan, Julia Philipp, Melissa Choz, A. W. K. Liu, Vikram Deshpande, Kristina Xega, Miguel Rivera, Joseph W. Franses, Johannes Kreuzer, Cyril H. Benes, Myriam Boukhali, Martin J. Aryee, Kevin D. Vo, Oliver Schilling, Francesco Marangoni, Matteo Ligorio, Adam Langenbucher, Sandra Misale, Srinjoy Sil, Michael S. Lawrence, Kshitij S. Arora, Wilhelm Haas, Linda T. Nieman, Vishal Thapar, Mihir Rajurkar, Chittampalli Yashaswini, Carlos Fernandez-del-Castillo, Cristina R. Ferrone, Niyati Desai, Elad Horwitz, David T. Ting, Shyamala Maheswaran, Ulrich F. Wellner, Neelima K.C. Magnus, Azfar Neyaz
Jazyk: angličtina
Rok vydání: 2019
Předmět:
pancreatic cancer
Mice
SCID
tumor architecture
single cell spatial analysis
Medical and Health Sciences
Mice
0302 clinical medicine
Cancer-Associated Fibroblasts
Stem Cell Research - Nonembryonic - Human
Mice
Inbred NOD
Tumor Microenvironment
2.1 Biological and endogenous factors
RNA-Seq
Aetiology
Cancer
mass spectrometry
0303 health sciences
education.field_of_study
Biological Sciences
single cell RNA-sequencing
Pancreatic Ductal
Heterografts
Female
Mitogen-Activated Protein Kinases
Carcinoma
Pancreatic Ductal
STAT3 Transcription Factor
Stromal cell
Epithelial-Mesenchymal Transition
pancreatic ductal adenocarcinoma
stromal microenvironment
Animals
Cell Proliferation
Coculture Techniques
HEK293 Cells
Humans
Pancreatic Neoplasms
Stromal Cells
Transfection
Population
Context (language use)
Biology
SCID
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Rare Diseases
Pancreatic cancer
Genetics
medicine
Epithelial–mesenchymal transition
education
030304 developmental biology
Tumor microenvironment
Carcinoma
Fibroblasts
Stem Cell Research
medicine.disease
Cancer cell
Cancer research
Inbred NOD
Digestive Diseases
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Cell
Cell, vol 178, iss 1
Popis: 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.
Databáze: OpenAIRE
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