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Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer.
Ligorio, Matteo; Sil, Srinjoy; Malagon-Lopez, Jose; Nieman, Linda T; Misale, Sandra; Di Pilato, Mauro; Ebright, Richard Y; Karabacak, Murat N; Kulkarni, Anupriya S; Liu, Ann; Vincent Jordan, Nicole; Franses, Joseph W; Philipp, Julia; Kreuzer, Johannes; Desai, Niyati; Arora, Kshitij S; Rajurkar, Mihir; Horwitz, Elad; Neyaz, Azfar; Tai, Eric; Magnus, Neelima K C; Vo, Kevin D; Yashaswini, Chittampalli N; Marangoni, Francesco; Boukhali, Myriam; Fatherree, Jackson P; Damon, Leah J; Xega, Kristina; Desai, Rushil; Choz, Melissa; Bersani, Francesca; Langenbucher, Adam; Thapar, Vishal; Morris, Robert; Wellner, Ulrich F; Schilling, Oliver; Lawrence, Michael S; Liss, Andrew S; Rivera, Miguel N; Deshpande, Vikram; Benes, Cyril H; Maheswaran, Shyamala; Haber, Daniel A; Fernandez-Del-Castillo, Carlos; Ferrone, Cristina R; Haas, Wilhelm; Aryee, Martin J; Ting, David T.
Affiliation
  • Ligorio M; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Sil S; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Malagon-Lopez J; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Nieman LT; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Misale S; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Di Pilato M; Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Ebright RY; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Karabacak MN; Cancer 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.
  • Kulkarni AS; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Liu A; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Vincent Jordan N; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Franses JW; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Philipp J; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Kreuzer J; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Desai N; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Arora KS; Cancer 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.
  • Rajurkar M; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Horwitz E; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Neyaz A; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Tai E; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Magnus NKC; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Vo KD; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Yashaswini CN; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Marangoni F; Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Boukhali M; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Fatherree JP; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Damon LJ; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Xega K; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Desai R; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Choz M; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Bersani F; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Langenbucher A; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Thapar V; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Morris R; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Wellner UF; Clinic of Surgery, UKSH Campus Lübeck, Germany.
  • Schilling O; Institute of Pathology, University Medical Center Freiburg, Germany.
  • Lawrence MS; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Liss AS; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Rivera MN; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Deshpande V; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Benes CH; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Maheswaran S; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Haber DA; Cancer 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.
  • Fernandez-Del-Castillo C; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Ferrone CR; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Haas W; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Aryee MJ; Cancer 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.
  • Ting DT; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: dting1@mgh.harvard.edu.
Cell ; 178(1): 160-175.e27, 2019 06 27.
Article in En | MEDLINE | ID: mdl-31155233
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Carcinoma, Pancreatic Ductal / Tumor Microenvironment / Cancer-Associated Fibroblasts Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2019 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Carcinoma, Pancreatic Ductal / Tumor Microenvironment / Cancer-Associated Fibroblasts Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2019 Document type: Article Affiliation country: Estados Unidos