Fibroblasts generate topographical cues that steer cancer cell migration

Baschieri, Francesco; Illand, Abigail; Barbazán, Jorge; Zajac, Olivier; Hénon, Clémence; Loew, Damarys; Dingli, Florent; Vignjević, Danijela; Lévêque‐Fort, Sandrine; Montagnac, Guillaume

doi:10.1101/2022.09.06.506801

Cited by 5 publications

(10 citation statements)

References 44 publications

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“…In the integrin β 3 transduced cells, it was challenging to identify specific FA structures due to the membrane localization of the probe, but distinct retraction fibers could be seen forming on the ECM coated portion of the substrate (Fig. 3D, Supplementary Video 6), demonstrating clear attachment to the ECM [44]. These results reveal that not only do Th1 cells possess all the necessary components to form FAs, but they only form these structure when ECM or adhesive ligands are present.…”

Section: Resultsmentioning

confidence: 99%

“…Ultimately, the difference between amoeboid and mesenchymal migration is blurry at best, as the mechanisms behind true integrin independent migration remain to be explored. Lastly, it is also likely that these FAs play important additional functional roles, such as leaving behind chemokine trails [48] or guiding other cells [44], and future work will be needed to decipher these important roles.…”

Section: Discussionmentioning

confidence: 99%

“…leaving behind a chemokine or degradation of the ECM) or physically (e.g. mechanical deformation of the ECM or membranous tubular network [44]). Either case implicates that FAs and their associated ECM play crucial roles in facilitating migration of Th1 cells through complex environments, beyond simply anchoring the cells to the substrate.…”

Section: Fn Provides Environmental Cues To Guide Migrationmentioning

confidence: 99%

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T cells Use Focal Adhesions to Pull Themselves Through Confined Environments

Caillier,

Oleksyn,

Fowell

et al. 2023

Preprint

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Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical composition. Their migration has classically been defined as amoeboid under the assumption that it is integrin-independent. Here we show that activated primary Th1 T cells require both confinement and extracellular matrix protein to migrate efficiently. This migration is mediated through small and dynamic focal adhesions that are composed of the same proteins associated with canonical mesenchymal focal adhesions, such as integrins, talin, and vinculin. These focal adhesions, furthermore, localize to sites of contractile traction stresses, enabling T cells to pull themselves through confined spaces. Finally, we show that Th1 T cell preferentially follows tracks of other T cells, suggesting that these adhesions are modifying the extracellular matrix to provide additional environmental guidance cues. These results demonstrate not only that the boundaries between amoeboid and mesenchymal migration modes are ambiguous, but that integrin-mediated adhesions play a key role in T cell motility.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Fn Provides Environmental Cues To Guide Migrationmentioning

confidence: 99%

See 1 more Smart Citation

T cells Use Focal Adhesions to Pull Themselves Through Confined Environments

Caillier,

Oleksyn,

Fowell

et al. 2023

Preprint

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“…5). This cooperative invasion strategy involving force transmission and microenvironmental cues bears striking resemblance to mechanisms observed in cancer progression 22,23,47 . The highly contractile, tip-like, leading CCM2 mutant ECs exhibit a competitive angiogenic advantage, allowing them to assert a stalk position upon neighboring wild-type ECs.…”

Section: Discussionmentioning

confidence: 74%

Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth

Shapeti,

Barrasa-Fano,

Fattah

et al. 2023

Preprint

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Force-driven cellular interactions are known to play a critical role in cancer cell invasion, but have remained largely unexplored in the context of vascular abnormalities, partly due to a lack of suitable genetic and cellular models. One such vascular abnormality, cerebral cavernous malformation (CCM) is characterized by leaky, tumor-like vessels in the brain, where CCM mutant cells recruit wild-type cells from the surrounding endothelium to form mosaic lesions and promote lesion growth; however the mechanisms underlying this recruitment remain poorly understood. Here, we use 3D traction force microscopy in a in-vitro model of early angiogenic invasion to reveal that hyper-angiogenic CCM2-silenced endothelial cells enhance angiogenic invasion of neighboring wild-type cells through force and extracellular matrix-guided mechanisms. We show that mechanically hyperactive CCM2-silenced tips guide wild-type cells by exerting and transmitting pulling forces and by leaving degraded paths in the matrix as cues promoting invasion in a ROCKs-dependent manner. This transmission of forces is associated with a reinforcement of β1 integrin-dependent adhesive sites and actin cytoskeleton in the wild-type followers. We also show that during this process wild-type cells are reprogrammed into stalk cells through activation of matrisome and DNA replication programs, eventually leading to cell proliferation. These observations unveil a novel vascular lesion growth mechanism where CCM2 mutants hijack the function of wild-type cells to fuel CCM lesion growth. By integrating biophysical computational methodologies to quantify cellular forces with advanced molecular techniques, we provide new insights in the etiology of vascular malformations, and open up avenues to study the role of cell mechanics in tissue heterogeneity and disease progression.

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“…In addition to tumor cells, other cells from the TME may be able to form collagen-tracks, such as cancer associated fibroblasts (CAFs). CAFs actively remodel the ECM, secrete multiple biologically active peptides, and have a high affinity for collagens 40,41 Together, these elements confer on them the potential to be major users of the collagen-track pathway, and points to the existence a new layer of interdependence in the microenvironment where the ECM serves as a platform for cell to cell communication regulating cancer cell invasion. Finally, we showed the presence of DDR1 along collagen fibers after cancer cell invasion in a mouse model, suggesting the presence of collagen-tracks in vivo.…”

Section: Discussionmentioning

confidence: 99%

Cancer cells transfer invasive properties through collagen-tracks

Saltel

Normand

Rouyer

et al. 2023

Preprint

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Invasion and migration through the extracellular matrix are prerequisites for metastasis, the leading cause of cancer-related deaths. During tumor development, the extracellular matrix is remodeled, including by overexpressing type I collagen that facilitate cancer dissemination. Most studies have focused on events at the leading edge as cells invade. We describe a new event at the trailing edge, as cells detach from the matrix. We show that small vesicles containing the collagen receptor DDR1 are left behind on collagen fibrils in the migration path. We named these structures attached to the collagen fibers "collagen-tracks". The vesicles are similar in size to exosomes but lack the exosome markers, and they also are different to migrasomes. We show that collagen-track formation is stimulated by DDR1 and by factors that promote adhesion, including collagen cross-linking. We report the protein, mRNA and miRNA content of collagen-tracks. They contain adhesion proteins, suggesting that they form when membrane fragments containing adhesions are torn from the cell as it migrates along collagen fibrils. We show that collagen-tracks are deposited by breast cancer cells in 3D matrices in vitro and in vivo. Collagen-tracks are stable and can be taken up by surrounding cells, promoting epithelial to mesenchymal transition, matrix degradation and invasion, finally leading to increased lung metastasis of breast cancer cells. In summary, we have identified and characterized a new vesicle entity directly attached to collagen fibrils that plays a role in cell-cell communication and can transfer invasive properties to surrounding cells. We conclude that cancer-related collagen-tracks are a new player acting locally to drive tumor invasion and metastasis

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Fibroblasts generate topographical cues that steer cancer cell migration

Cited by 5 publications

References 44 publications

T cells Use Focal Adhesions to Pull Themselves Through Confined Environments

T cells Use Focal Adhesions to Pull Themselves Through Confined Environments

Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth

Cancer cells transfer invasive properties through collagen-tracks

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