Evidence map›Paper›PMID 31155233›Full record

ArticleCell2019

Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer.

Matteo Ligorio, Srinjoy Sil, Jose Malagon-Lopez, Linda T Nieman, Sandra Misale, Mauro Di Pilato, Richard Y Ebright, Murat N Karabacak, Anupriya S Kulkarni, Ann Liu and 38 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 364 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
364citing papers in PubMed, 1 pooled it
33.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

364 citing papers in PubMed, 1 synthesis or guideline pooled it, 527 citations in OpenAlex.

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304 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

48 authors at 5 institutions in 2 countries.

Matteo LigorioCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Srinjoy SilCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Jose Malagon-LopezCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Linda T NiemanCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Sandra MisaleCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Mauro Di PilatoDivision of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
Richard Y EbrightCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Murat N KarabacakCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02114, USA.
Anupriya S KulkarniCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Ann LiuCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Nicole Vincent JordanCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Joseph W FransesCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Julia PhilippCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Johannes KreuzerCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Niyati DesaiCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Kshitij S AroraCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Mihir RajurkarCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Elad HorwitzCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Azfar NeyazCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Eric TaiCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Neelima K C MagnusCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Kevin D VoCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Chittampalli N YashaswiniCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Francesco MarangoniDivision of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
Myriam BoukhaliCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Jackson P FatherreeCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Leah J DamonCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Kristina XegaCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Rushil DesaiCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Melissa ChozCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Francesca BersaniCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Adam LangenbucherCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Vishal ThaparCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Robert MorrisCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Ulrich F WellnerClinic of Surgery, UKSH Campus Lübeck, Germany.
Oliver SchillingInstitute of Pathology, University Medical Center Freiburg, Germany.
Michael S LawrenceCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Andrew S LissDepartment of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Miguel N RiveraCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Vikram DeshpandeCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Cyril H BenesCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Shyamala MaheswaranCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Daniel A HaberCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Carlos Fernandez-Del-CastilloCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Cristina R FerroneCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Wilhelm HaasCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Martin J AryeeCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: aryee.martin@mgh.harvard.edu.
David T TingCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: dting1@mgh.harvard.edu.
Massachusetts General Hospital · USHarvard University · USHoward Hughes Medical Institute · USUniversitäres Kinderwunschzentrum Lübeck · DEUniversity Medical Center Freiburg · DE

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
MOUNT SINAI MEDICAL SCIENTIST TRAINING PROGRAMT32GM007280 · NIGMS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BARON, MARGARET H · 1985 to 2021
$22.8M
Point-of care Microfluidics for Early Detection of CancerU01EB012493 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., TONER, MEHMET · 2010 to 2018
$19.6M
Training Program in Cancer Biology and TherapeuticsT32CA071345 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber, Lecia V. Sequist · 1997 to 2026
$10.6M
Modeling Metastasis and Acquired Drug Resistance Using Circulating Tumor CellsR01CA129933 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber · 2008 to 2026
$7.5M
Systems approaches to understanding the relationships between genotype, signaling, and therapeutic efficacyU01CA215798 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HAAS, WILHELM, HAIGIS, KEVIN · 2017 to 2021
$3.7M
Mechanistic Understanding for the Role of Lin28b in Pancreatic Cancer ProgressionR01CA235412 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI EL-BARDEESY, NABEEL, MOSTOSLAVSKY, RAUL · 2019 to 2023
$3.2M
Metastasis and biophysics of clusters of circulating tumor cells in the microcirculationU01CA214297 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., MAHESWARAN, SHYAMALA · 2018 to 2022
$2.9M
Genome-scale CRISPR activation screening to identify lung-specific metastatic pathwaysF30CA232407 · NCI · HARVARD MEDICAL SCHOOL · PI EBRIGHT, RICHARD · 2018 to 2020
$118k
Howard Hughes Medical InstituteNCI NIH HHS F30 CA232407NCI NIH HHS R01 CA129933NCI NIH HHS R01 CA235412NCI NIH HHS T32 CA071345NCI NIH HHS U01 CA214297NCI NIH HHS U01 CA215798NIBIB NIH HHS U01 EB012493NIGMS NIH HHS T32 GM007280NIGMS NIH HHS T32 GM007753
6 · The paper itself

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.

Indexed as

Tumor MicroenvironmentAnimalsCancer-Associated FibroblastsCarcinoma, Pancreatic DuctalCell ProliferationCoculture TechniquesEpithelial-Mesenchymal TransitionFemaleHEK293 CellsHeterograftsHumansMiceMice, Inbred NODMice, SCIDMitogen-Activated Protein KinasesPancreatic NeoplasmsMitogen-Activated Protein KinasesSTAT3 protein, humanSTAT3 Transcription Factormass spectrometrypancreatic cancerpancreatic ductal adenocarcinomasingle cell RNA-sequencingsingle cell spatial analysisstromal microenvironmenttumor architecture

Identifiers

PMID31155233
PMCPMC6697165
OpenAlexW2947548345

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.