2022
DOI: 10.1101/2022.09.06.506801
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Fibroblasts generate topographical cues that steer cancer cell migration

Abstract: Fibroblasts play a fundamental role in tumor development. Among other functions, they regulate cancer cells migration through rearranging the extracellular matrix, secreting soluble factors and establishing direct physical contacts with cancer cells. Here, we report that migrating fibroblasts deposit on the substrate a network of tubular structures that serves as guidance cue for cancer cell migration. Such membranous tubular network, hereafter called tracks, is stably anchored to the substrate in a β5 integri… Show more

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Cited by 5 publications
(10 citation statements)
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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%
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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%
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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%
“…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%