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Deconstructing tumor heterogeneity: the stromal perspective

2020; Impact Journals LLC; Volume: 11; Issue: 40 Linguagem: Inglês

10.18632/oncotarget.27736

1949-2553

Renee E. Vickman, Douglas V. Faget, Philip A. Beachy, David J. Beebe, Neil A. Bhowmick, Edna Cukierman, Wu-Min Deng, James G. Granneman, Jeffrey Hildesheim, Raghu Kalluri, Ken S. Lau, Ernst Lengyel, Joakim Lundeberg, Jorge Moscat, Peter S. Nelson, Kristian Pietras, Katerina Politi, Ellen Puré, Ruth Scherz‐Shouval, Mara H. Sherman, David A. Tuveson, Ashani T. Weeraratna, Richard M. White, Melissa H. Wong, Elisa C. Woodhouse, Ying Zheng, Simon W. Hayward, Sheila A. Stewart,

Cancer Cells and Metastasis

// Renee E. Vickman 1 , * , Douglas V. Faget 2 , * , Philip Beachy 3 , David Beebe 4 , Neil A. Bhowmick 5 , Edna Cukierman 6 , Wu-Min Deng 7 , James G. Granneman 8 , Jeffrey Hildesheim 9 , Raghu Kalluri 10 , Ken S. Lau 11 , Ernst Lengyel 12 , Joakim Lundeberg 13 , Jorge Moscat 14 , Peter S. Nelson 15 , Kristian Pietras 16 , Katerina Politi 17 , Ellen Puré 18 , Ruth Scherz-Shouval 19 , Mara H. Sherman 20 , David Tuveson 21 , Ashani T. Weeraratna 22 , Richard M. White 23 , Melissa H. Wong 20 , Elisa C. Woodhouse 9 , Ying Zheng 24 , Simon W. Hayward 1 , # and Sheila A. Stewart 2 , # 1 Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA 2 Department of Cell Biology and Physiology, Washington University in St. Louis, St. Louis, MO, USA 3 Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA 4 Department of Biomedical Engineering, University of Wisconsin – Madison, Madison, WI, USA 5 Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA 6 Department of Cancer Biology, Marvin and Concetta Greenberg Pancreatic Cancer Institute, Fox Chase Cancer Center, Temple Health, Philadelphia, PA, USA 7 Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA 8 Department of Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA 9 National Cancer Institute, Bethesda, MD, USA 10 Department of Cancer Biology, MD Anderson Cancer Center, Houston, TX, USA 11 Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA 12 Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, USA 13 SciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden 14 Weill Cornell Medicine, Rockefeller University Campus, New York, NY, USA 15 Department of Medicine, University of Washington, Seattle, WA, USA 16 Department of Laboratory Medicine, Lund University, Lund, Sweden 17 Department of Pathology, Yale University School of Medicine, New Haven, CT, USA 18 Department of Biomedical Sciences, University of Pennsylvania, Philidelphia, PA, USA 19 Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, Israel 20 Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR, USA 21 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA 22 Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA 23 Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA 24 Department of Bioengineering, University of Washington, Seattle, WA, USA * These authors contributed equally to this work # Workshop co-chairs Correspondence to: Jeffrey Hildesheim, email: hildesheimj@mail.nih.gov Elisa C. Woodhouse, email: woodhousee@mail.nih.gov Keywords: tumor microenvironment; stromal heterogeneity; extracellular matrix; cellular plasticity; therapy resistance Received: August 19, 2020 Accepted: August 24, 2020 Published: October 06, 2020 Copyright: © 2020 Vickman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Significant advances have been made towards understanding the role of immune cell-tumor interplay in either suppressing or promoting tumor growth, progression, and recurrence, however, the roles of additional stromal elements, cell types and/or cell states remain ill-defined. The overarching goal of this NCI-sponsored workshop was to highlight and integrate the critical functions of non-immune stromal components in regulating tumor heterogeneity and its impact on tumor initiation, progression, and resistance to therapy. The workshop explored the opposing roles of tumor supportive versus suppressive stroma and how cellular composition and function may be altered during disease progression. It also highlighted microenvironment-centered mechanisms dictating indolence or aggressiveness of early lesions and how spatial geography impacts stromal attributes and function. The prognostic and therapeutic implications as well as potential vulnerabilities within the heterogeneous tumor microenvironment were also discussed. These broad topics were included in this workshop as an effort to identify current challenges and knowledge gaps in the field.