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Role of the Extracellular Matrix in Tumor Stroma: Barrier or Support?

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Biomarkers of the Tumor Microenvironment

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Abstract

Extensive evidence exists to functionally implicate stromal cancer-associated fibroblasts in tumor progression. Data from experimental cancer models has questioned the exclusive tumor-supportive function of the tumor stroma and suggested that the stroma might also act as a barrier to inhibit tumor metastasis. With consideration of this shift in dogma, we discuss the role of a specific part of the tumor stroma, the insoluble extracellular matrix (ECM), in tumor growth and spread. We summarize data from experimental tumor models on the role of fibrillar collagens, the fibronectin EDA splice form, proteoglycans, and the matricellular proteins, periostin and tenascins, which are all major components of the tumor stroma. In addition to the composition of the ECM being able to regulate tumorigenesis via integrin-mediated signaling, recent data indicate that the stiffness of the ECM also significantly impacts tumor growth and progression. These two properties add to the complexity of tumor-stroma interactions and have significant implications for gene regulation, matrix remodeling, and tumor metastasis. The role of the tumor stroma is thus extremely complex and highlights the importance of relating findings to tumor-type-, tissue-, and stage-specific effects in addition to considering inter-tumor and intra-tumor heterogeneity. Further work is needed to determine the relative contribution of different ECM proteins to the tumor-supporting and tumor-inhibiting roles of the tumor stroma.

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Acknowledgments

We acknowledge the useful comments from Sandy Der (University Health Network, Toronto).

Supported by grants to DG from the Research Council of Norway (Norwegian Centres of Excellence grant, grants 2233250), the Western Norway Regional Health Authority (ID911899), and the Norwegian Cancer Society (id 3292722 to MKG).

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Authors and Affiliations

  1. Princess Margaret Cancer Centre, University Health Network, Princess Margaret Cancer Research Tower, 101 College Street, 14th Floor, Room 14-301, Toronto, ON, M5G 1L7, Canada

    Cédric Zeltz

  2. Princess Margaret Cancer Centre, University Health Network, Princess Margaret Cancer Research Tower, 101 College Street, 14th Floor, Room 14-301C, Toronto, ON, M5G 1L7, Canada

    Roya Navab

  3. Department of Biomedicine, University of Bergen, Bergen, Norway

    Marion Kusche-Gullberg & Donald Gullberg

  4. Princess Margaret Cancer Centre, University Health Network, Departments of Laboratory Medicine, Pathobiology and Medical Biophysics, University of Toronto, Princess Margaret Cancer Research Tower, 101 College Street, 14th Floor, Room 14-305, Toronto, ON, M5G 1L7, Canada

    Ming-Sound Tsao

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  1. Cédric Zeltz
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  2. Roya Navab
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  3. Marion Kusche-Gullberg
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  4. Ming-Sound Tsao
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  5. Donald Gullberg
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Correspondence to Donald Gullberg .

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Editors and Affiliations

  1. Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Lars A. Akslen

  2. Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Randolph S. Watnick

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Zeltz, C., Navab, R., Kusche-Gullberg, M., Tsao, MS., Gullberg, D. (2017). Role of the Extracellular Matrix in Tumor Stroma: Barrier or Support?. In: Akslen, L., Watnick, R. (eds) Biomarkers of the Tumor Microenvironment. Springer, Cham. https://doi.org/10.1007/978-3-319-39147-2_4

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