A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy

Cancer cells disseminate and seed in distant organs, where they can remain dormant for many years before forming clinically detectable metastases. Here we studied how disseminated tumor cells sense and remodel the extracellular matrix (ECM) to sustain dormancy. ECM proteomics revealed that dormant cancer cells assemble a type III collagen-enriched ECM niche. Tumor-derived type III collagen is required to sustain tumor dormancy, as its disruption restores tumor cell proliferation through DDR1-mediated STAT1 signaling. Second-harmonic generation two-photon microscopy further revealed that the dormancy-to-reactivation transition is accompanied by changes in type III collagen architecture and abundance. Analysis of clinical samples revealed that type III collagen levels were increased in tumors from patients with lymph node-negative head and neck squamous cell carcinoma compared to patients who were positive for lymph node colonization. Our data support the idea that the manipulation of these mechanisms could serve as a barrier to metastasis through disseminated tumor cell dormancy induction. Bravo-Cordero and colleagues demonstrate that disseminated tumor cells remodel the extracellular matrix by secreting collagen III and generate a stromal architecture that favors dormancy through DDR1 and STAT1 signaling.

Automated summary

Cancer cells disseminate and seed in distant organs, remaining dormant before forming detectable metastases. Research shows that dormant cancer cells assemble an ECM niche enriched with type III collagen, which is essential for sustaining tumor dormancy. Disruption of tumor-derived type III collagen can restore tumor cell proliferation and lead to dormancy-to-reactivation transition.