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

  • Cédric Zeltz
  • Roya Navab
  • Marion Kusche-Gullberg
  • Ming-Sound Tsao
  • Donald Gullberg


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.


Tumor microenvironment Tumor stroma Extracellular matrix Fibrillar collagen Tumor growth Tumor metastasis Tumor stiffness Lysyl oxidase Fibronectin EDA Periostin Tenascins Proteoglycans 



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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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Cédric Zeltz
    • 1
  • Roya Navab
    • 2
  • Marion Kusche-Gullberg
    • 3
  • Ming-Sound Tsao
    • 4
  • Donald Gullberg
    • 3
  1. 1.Princess Margaret Cancer CentreUniversity Health NetworkTorontoCanada
  2. 2.Princess Margaret Cancer CentreUniversity Health NetworkTorontoCanada
  3. 3.Department of BiomedicineUniversity of BergenBergenNorway
  4. 4.Princess Margaret Cancer Centre, University Health Network, Departments of Laboratory MedicinePathobiology and Medical Biophysics, University of Toronto, Princess Margaret Cancer Research TowerTorontoCanada

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