PerspectiveCANCER

The tumor as organizer model

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Science  08 Mar 2019:
Vol. 363, Issue 6431, pp. 1038-1039
DOI: 10.1126/science.aau9861

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  • RE: The tumor as organizer model
    • Peter B. Vermeulen, Pathologist, GZA Hospitals Antwerp & University of Antwerp, Antwerp, Belgium
    • Other Contributors:
      • Elizabeth A. Kuczynski, Postdoctoral Fellow, Bioscience, Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom
      • Andrew R Reynolds, Principal Medical Scientist, Oncology Translational Medicine Unit, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom
      • Francesco Pezzella, Pathologist, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospit
      • Robert S. Kerbel, Senior Scientist, Biological Sciences Platform, Sunnybrook Research Institute & Department of Medical Biophysics, University of Toronto, Canada
      • Luc Y. Dirix, Medical Oncologist, GZA Hospitals Antwerp, Antwerp, Belgium

    The tissue microenvironment can also act as a tumor organizer

    In their recent article “The tumor as organizer model” Li and Stanger argue that cancer cells are the principle organizers of their tumor microenvironment (TME) (1). We believe that this is an oversimplification. This is because some tumors do not induce new stroma but rather co-opt and preserve the pre-existing microenvironmental structures of the tissues they colonize, suggesting that the pre-existing tissue microenvironment can also act as a ‘tumor organizer.’

    In the embryo, a small number of organizer cells determine the structure of the entire embryo by influencing neighboring cells to change fate. Li and Stanger propose an analogous ‘tumor as organizer’ model in which a developing tumor is the primary architect of its microenvironment, which ultimately leads to disorganized and heterogenous tumors. A counterpoint to the ‘tumor as organizer’ concept is the histopathological observation that many tumors demonstrate well-organized patterns of growth that appear to be determined by the tissue microenvironment (2). As an example, both primary lung tumors and lung metastases can grow by filling the alveolar air spaces while preserving the alveolar walls within the tumor. Similarly, cancer cells of liver metastases can replace the hepatocytes while preserving the intervening sinusoidal blood vessels and connective tissue. In both scenarios, the tumors preserve the tissue stromal morphology which pe...

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    Competing Interests: None declared.
  • RE: The tumor as organizer model

    The Tumor as Part of the Organizer Model

    In the article, “The tumor as organizer model,” Li and Stanger (2019) describe a reductionist model where tumor cells reside at the apex of a tumor microenvironment (TME) hierarchy. I suggest this is only one part of a larger model involving a complex of nested feedback loops (Brandman and Meyers, 2008), in what Bissell described as a state of dynamic reciprocity (Nelson and Bissell, 2005) between the TME and the surrounding extracellular matrix and microenvironment (ECM-M). A complexity of events on differing time scales between the TMA and ECM-M involves many mechanisms, including physical and chemical interactions (Ricca et al, 2018) that underlie this system of nested feedback loops. The lack of T cell infiltration in some tumors, for example, involves interactions between the TME and the ECM-M. “Checkpoint inhibitors” block this interaction (Wei et al, 2018). That fiber contained in dietary vegetables and grains has even been shown to facilitate the effectiveness of checkpoint inhibitors (Spencer et al, 2019) argues that the TME is but one nest in the complex system. The result of Spencer et al (2019) makes good sense, because “checkpoint inhibitors” renormalize our immune system, especially T-cells that naturally attack the cancer, and we know that fiber acting in the gut regulate T-cells in our immune system (Trompette et al (2018). Thus eating a high fiber diet enhances T-cell metabolism, and the checkpoint inhibitor...

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    Competing Interests: Dr. Maguire has equity in NeoGenesis Inc

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