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CANCER BIOLOGY

Pulling the strings of tumor collagen

Nature Cancer volume 3, pages 9–10 (2022)Cite this article

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The architecture of tumor collagen greatly influences tumor biology and therapeutic response. Two new studies identify tumor DDR1 as a central player in stromal collagen deposition and organization in the primary tumor and in disseminated tumor cells, resulting in immune exclusion or sustained dormancy, respectively.

The tumor microenvironment, including its resident cells and structural components such as collagen fibers, influence cancer progression, metastasis and response to treatment1. The composition, architecture and organization of collagen fibers has been directly linked to the potential of cancer cells to acquire invasive abilities for local cancer invasion and distant metastasis. Different classes of tumor-associated collagen signatures can be discriminated, some of which correlate with disease-free survival in patients with cancer2. However, little is known about the mechanisms that underpin the formation and maintenance of differently organized collagen fibers surrounding cancer cells. Two recent studies now put the collagen-binding receptor tyrosine kinase discoidin domain receptor 1 (DDR1) on center stage as a key regulator of tumor collagen organization in the primary tumor and in disseminated cancer cells. First, in this issue of Nature Cancer, Di Martino et al. show that DDR1 regulates disseminated tumor cells (DTCs) by secreting collagen type III, which generates a ‘wavy’ collagen architecture that favors dormancy3. Second, in a separate study published in Nature, Sun et al. demonstrate that tumor DDR1 organizes a highly ordered and impenetrable collagen matrix that leads to immune exclusion in triple-negative breast cancer4. The two studies provide complementary insights into the crucial roles of DDR1 in cancer biology at different stages of tumor progression.

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Fig. 1: A central role for tumor DDR1 in organizing stromal collagen architecture.

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  1. National Heart and Lung Institute, Imperial College London, London, UK

    Birgit Leitinger

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  1. Birgit Leitinger
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Correspondence to Birgit Leitinger.

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Leitinger, B. Pulling the strings of tumor collagen. Nat Cancer 3, 9–10 (2022). https://doi.org/10.1038/s43018-021-00323-4

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