Metastatic Tumor Cells Exploit Their Adhesion Repertoire to Counteract Shear Forces during Intravascular Arrest

Epithelial–mesenchymal transitions (EMTs) generate hybrid phenotypes with an enhanced ability to adapt to diverse microenvironments encountered during the metastatic spread. Accordingly, EMTs play a crucial role in the biology of circulating tumor cells (CTCs) and contribute to their heterogeneity. Here, we review major EMT-driven properties that may help hybrid Epithelial/Mesenchymal CTCs to survive in the bloodstream and accomplish early phases of metastatic colonization. We then discuss how interrogating EMT in CTCs as a companion biomarker could help refine cancer patient management, further supporting the relevance of CTCs in personalized medicine.

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“…. ) enabling their adherence to the endothelium [223], fibrin or platelets may indeed also mediate and strengthen such interactions [224,225].…”

Section: Activation Of Coagulationmentioning

confidence: 99%

EMT-Associated Heterogeneity in Circulating Tumor Cells: Sticky Friends on the Road to Metastasis

Genna

Vanwynsberghe

Villard

et al. 2020

Cancers

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“…Recent findings link the expression of different CD44 isoform variants with cancer progression and specific tumor cell features, including pro-survival signaling [37], cellular reprogramming [38], acquisition of migratory capacity [39], and tumor initiation [40,41,42]. CD44 can also facilitate the arrest of circulating tumor cells prior to extravasation [43]. Together, these findings emphasize the cellular and molecular heterogeneity that exists within cancer cell populations, which belie the power of bulk population analyses to define putative therapeutic options.…”

Section: Cancer Cell Heterogeneity: a Hierarchical Matter?mentioning

confidence: 99%

“…In order to reach secondary sites, circulating tumor cells (CTCs) have to avoid the hostile blood or lymphatic flow forces to arrest and stably adhere to the endothelium of the target organ [157,158]. CTC-extrinsic mechanisms such hemodynamic forces have been proven to be key in CTC endothelial arrest and extravasation [43,159]. We have recently identified a threshold of hemodynamic forces that allow stable arrest of CTCs in low-flow venous-like vascular regions, and active endothelial remodeling in higher-flow regions.…”

Section: The Seed the Journey And The Soil: The Metastatic Cascadementioning

confidence: 99%

“…Those findings have provided motivation to consider mechanical properties as a possible biomarker for cancer cell stemness. Indeed, we have recently shown that CD44 plays a key role in early endothelial arrest, as CD44 mediates the early weak-magnitude adhesion forces required for CTC arrest at the endothelial wall [43]. Hence, the increased metastatic potential of CTC clusters could be explained in part by a higher propensity to arrest on endothelial cells and to extravasate, which might be directly linked to the cell deformability index of CTC clusters.…”

Section: The Seed the Journey And The Soil: The Metastatic Cascadementioning

confidence: 99%

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The Complexities of Metastasis

Juan

Garcia‐Leon

Rangel

et al. 2019

Cancers

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Therapies that prevent metastatic dissemination and tumor growth in secondary organs are severely lacking. A better understanding of the mechanisms that drive metastasis will lead to improved therapies that increase patient survival. Within a tumor, cancer cells are equipped with different phenotypic and functional capacities that can impact their ability to complete the metastatic cascade. That phenotypic heterogeneity can be derived from a combination of factors, in which the genetic make-up, interaction with the environment, and ability of cells to adapt to evolving microenvironments and mechanical forces play a major role. In this review, we discuss the specific properties of those cancer cell subgroups and the mechanisms that confer or restrict their capacity to metastasize.

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“…The arrest of MCC on vascular surface depends on the physical restriction of capillaries [37], or on active adhesive processes involving selectins, integrins, cadherins, CD44 and immunoglobulin superfamily receptors [39,40].…”

Section: Ros Functionmentioning

confidence: 99%

The role of redox system in metastasis formation

et al. 2021

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The metastatic cancer disease represents the real and urgent clinical need in oncology. Therefore, an understanding of the complex molecular mechanisms sustaining the metastatic cascade is critical to advance cancer therapies. Recent studies highlight how redox signaling influences the behavior of metastatic cancer cells, contributes to their travel in bloodstream from the primary tumor to the distant organs and conditions the progression of the micrometastases or their dormant state. Radical oxygen species not only regulate intracellular processes but participate to paracrine circuits by diffusion to nearby cells, thus assuming unpredicted roles in the communication between metastatic cancer cells, blood circulating cells, and stroma cells at site of colonization. Here, we review recent insights in the role of radical oxygen species in the metastasis formation with a special focus on extravasation at metastatic sites.

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Metastatic Tumor Cells Exploit Their Adhesion Repertoire to Counteract Shear Forces during Intravascular Arrest

Abstract: Highlights d Metastatic cells have higher adhesion ability d Low-energy adhesions initiate transient intravascular arrest d Stronger adhesions mediate stable CTC/endothelium bonds and extravasation d Flow-dependent deposition of luminal fibronectin favors CTC intravascular arrest

Cited by 96 publications

References 51 publications

EMT-Associated Heterogeneity in Circulating Tumor Cells: Sticky Friends on the Road to Metastasis

EMT-Associated Heterogeneity in Circulating Tumor Cells: Sticky Friends on the Road to Metastasis

The Complexities of Metastasis

The role of redox system in metastasis formation

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