![]() Solid stress is a consequence of the proliferation of cancer cells against a viscoelastic boundary, the stroma, which resists tumor growth and prevents its expansion, resulting in the buildup of internal pressure 3, 4. Cancer cells continuously sense signals from the surroundings that could be either biochemical, such as soluble molecules or membrane receptors on stromal cells, or physical, including stiffness, the microarchitecture of the surrounding extracellular matrix (ECM), fluid pressure and solid stress 2. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.Ĭancer progression is the result of complex interactions between cancer cells and their microenvironment 1. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP and a decrease in proliferation. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. ![]() Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells.
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