Cancer cell motility: lessons from migration in confined spaces

Paul, Colin D.; Mistriotis, Panagiotis; Κωνσταντόπουλος, Κωνσταντίνος

doi:10.1038/nrc.2016.123

Cited by 486 publications

(450 citation statements)

References 132 publications

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“…Work examining cell migration and invasion in confined extracellular matrix and cellular in vitro and in vivo environments has revealed that cells harbor a remarkable repertoire of strategies to move through restrictive barriers, including shifts between amoeboid and mesenchymal migration, the ability to withstand nuclear envelope rupture, and even osmotic and nuclear-piston driven cell movement (Paul et al, 2017). Because of the challenges of examining cell size during the dynamic process of tissue invasion, however, it was not known if invasive cells can dynamically modulate membrane area and cell volume to enter tissues.…”

Section: Discussionmentioning

confidence: 99%

Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain

et al. 2017

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Summary Invasive cells use small invadopodia to breach basement membrane (BM), a dense matrix that encases tissues. Following the breach, a large protrusion forms to clear a path for tissue entry by poorly understood mechanisms. Using RNAi screening for defects in C. elegans anchor cell (AC) invasion, we found that UNC-6(netrin)/UNC-40(DCC) signaling at the BM breach site directs exocytosis of lysosomes using the exocyst and SNARE SNAP-29 to form a large protrusion that invades vulval tissue. Live-cell imaging revealed that the protrusion is enriched in the matrix metalloprotease ZMP-1 and transiently expands AC volume more than 20%, displacing surrounding BM and vulval epithelium. Photobleaching and genetic perturbations showed that the BM receptor dystroglycan forms a membrane diffusion barrier at the neck of the protrusion that enables protrusion growth. Together these studies define a netrin dependent pathway that builds an invasive protrusion, an isolated lysosome-derived membrane structure specialized to breach tissue barriers.

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Section: Discussionmentioning

confidence: 99%

Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain

et al. 2017

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“…Advancements in time-lapse, deep-tissue imaging using intravital microscopy have demonstrated the importance of tumor cell migration in vivo [245]. Invasion through the genesis of invadopodia illustrate a dependence on prostaglandin signaling [246].…”

Section: Hematogenous Spread Extravasation and Secondary Site Metastmentioning

confidence: 99%

Platelet “first responders” in wound response, cancer, and metastasis

Menter

Kopetz

Hawk

et al. 2017

Cancer Metastasis Rev

138

115

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Platelets serve as “First Responders” during normal wounding and homeostasis. Arising from bone marrow stem cell lineage megakaryocytes, anucleate platelets can influence inflammation and immune regulation. Biophysically, platelets are optimized due to size and discoid morphology to distribute near vessel walls, monitor vascular integrity and initiate quick responses to vascular lesions. Adhesion receptors linked to a highly reactive filopodia-generating cytoskeleton maximizes their vascular surface contact allowing rapid response capabilities. Functionally, platelets normally initiate rapid clotting, vasoconstriction, inflammation and wound biology that leads to sterilization, tissue repair and resolution. Platelets also are among the first to sense, phagocytize, decorate, or react to pathogens in the circulation. These platelet first responder properties are commandeered during chronic inflammation, cancer progression and metastasis. Leaky or inflammatory reaction blood vessel genesis during carcinogenesis provides opportunities for platelet invasion into tumors. Cancer is thought of as a non-healing or chronic wound that can be actively aided by platelet mitogenic properties to stimulate tumor growth. This growth ultimately outstrips circulatory support leads to angiogenesis and intravasation of tumor cells into the blood stream. Circulating tumor cells reengage additional platelets, which facilitates tumor cell adhesion, arrest and extravasation and metastasis. This process, along with the hypercoagulable states associated with malignancy is amplified by IL6 production in tumors that stimulate liver thrombopoietin production and elevates circulating platelet numbers by thrombopoiesis in the bone marrow. These complex interactions and the “First Responder” role of platelets during diverse physiologic stresses provides a useful therapeutic target that deserves further exploration.

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“…Tumor cells also use aligned fibrillar structures for rapid and widespread dissemination from the primary site (56). In the case of breast cancer, radially aligned .…”

Section: Discussionmentioning

confidence: 99%

“…For in vitro studies, surface cues such as microgrooves, ridges, and patterned substrates have been used to show that cells modulate signaling cascades and gene expression in 2D platforms in response to topography (56,57). Additionally, naturally derived ECMs such as collagen and fibrin can be used to form diverse fibrillar architectures in 3D hydrogels (58).…”

Section: Cc-by-nc-mentioning

confidence: 99%

Probing cellular response to topography in three dimensions

Paul

Hruska

Staunton

et al. 2017

Preprint

Self Cite

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Biophysical aspects of in vivo tissue microenvironments include microscale mechanical properties, fibrillar alignment, architecture or topography of the extracellular matrix (ECM), and the repertoire of ECM ligands present, all of which provide cues to drive cellular response. Cell-ECM interactions are important regulators of both normal tissue homeostasis and malignancy.Thus, understanding both extracellular cues and the cellular responses they elicit is fundamental to developing therapeutic strategies. Various in vitro platforms for 3D cell culture and tissue engineering have been used to study cellular response to the microenvironment. However, recapitulating the diversity of tissue architectures present in vivo in a controlled manner in threedimensional tissue mimetics is challenging using naturally derived ECM hydrogels. Here, we use a bottom-up approach to build fibrillar architecture into 3D amorphous hydrogels using selfassembly of magnetic colloidal particles functionalized with human ECM proteins. Human ECM proteins associated with organ-specific pathological states were used. We determined that, while the bulk tissue mechanics of hydrogels containing either aligned fibers or randomly distributed colloidal particles were similar, aligned hydrogels exhibited spatial heterogeneities in microscale mechanical properties near aligned fibers. We then used this platform in combination with 2D substrates of defined elastic modulus to decouple the role of topography from microscale tissue mechanics for normal and tumor cells. We determined that topographical cues dominate cellular response for human and normal cells, which responded independently of microscale mechanics and ECM composition in 3D hydrogels. These data suggest that topography alone can drive fundamental cellular responses such as polarization and migration for both normal and transformed cells.

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Cancer cell motility: lessons from migration in confined spaces

Cited by 486 publications

References 132 publications

Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain

Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain

Platelet “first responders” in wound response, cancer, and metastasis

Probing cellular response to topography in three dimensions

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