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Article Dans Une Revue Nature Reviews Cancer Année : 2019

Fluids and their mechanics in tumour transit: shaping metastasis

Résumé

The Greek phrase 'Panta Rhei' , which literally translates as 'everything flows' , is a philosophical concept that is often attributed to the presocratic Greek philosopher Heraclitus (circa 500 bc) and was an attempt to explain the ever-changing nature of life. Work over the past decades has shown that this notion might also apply to tumour metastasis, a complex multistep process whereby malignant tumours shed invasive cells with metastatic capacity that need to overcome many obstacles (for example, immune surveillance) for successful outgrowth at secondary sites 1. However, in addition to the multiple molecular pathways driving metastasis, a plethora of studies conducted over the past two decades strongly suggest that mechanical forces are also responsible for tumour progression and response to classical therapies 2-4. Among these forces, fluid-based mechanics have progressively entered the scene. Indeed, on their way to forming a metastasis, tumour cells and tumour-secreted factors use and exploit three main bodily fluids-blood, lymph and interstitial fluid 5-7 (Fig. 1a). Circulating tumour cells (CTCs) and their associated material, including soluble factors and extracellular vesicles (EVs), can directly travel through the haematogenous system 1,8 or sequentially use both the lymphatic and blood vasculature to colonize distant organs 9-11 (Fig. 1b). This notion that fluid-based mechanics can shape metastasis originated from an early pivotal study that coined the 'hemodynamic theory' , which showed that arterial blood flow in certain organs can be positively correlated with the frequency and patterns of metasta-sis 12 , supporting a link between flow mechanics and the secondary site of metastasis. When transported in fluids, CTCs are subjected to and exploit various mechanical forces, which can influence their fate in many ways. For instance, high shear forces exerted on CTCs can induce mechanical stress, leading to cell fragmentation and death 13 , whereas intermediate shear forces have been shown to favour CTC intravascular arrest and extravasation 14. Thus, an improved understanding of the mechanical forces encountered by CTCs and tumour-associated material in fluids is crucial for fully elucidating the metastatic cascade and delineating vulnerable CTC states for therapeutic intervention. In this Review, we describe how circulating tumour-derived material (cells and associated factors) use bodily fluids, their underlying forces and the resultant stresses they impose as a natural means to escape from primary tumours, travel throughout the body, prime pre-metastatic niches (PMNs) and successfully seed distant metastases. We briefly discuss key flow-related aspects of tumour growth and invasion that have received considerable attention 2,6,7 and discuss how these modes of flow are essential means of transport Fluids and their mechanics in tumour transit: shaping metastasis Abstract | Metastasis is a dynamic succession of events involving the dissemination of tumour cells to distant sites within the body , ultimately reducing the survival of patients with cancer. To colonize distant organs and, therefore, systemically disseminate within the organism, cancer cells and associated factors exploit several bodily fluid systems, which provide a natural transportation route. Indeed, the flow mechanics of the blood and lymphatic circulatory systems can be co-opted to improve the efficiency of cancer cell transit from the primary tumour, extravasation and metastatic seeding. Flow rates, vessel size and shear stress can all influence the survival of cancer cells in the circulation and control organotropic seeding patterns. Thus, in addition to using these fluids as a means to travel throughout the body , cancer cells exploit the underlying physical forces within these fluids to successfully seed distant metastases. In this Review , we describe how circulating tumour cells and tumour-associated factors leverage bodily fluids, their underlying forces and imposed stresses during metastasis. As the contribution of bodily fluids and their mechanics raises interesting questions about the biology of the metastatic cascade, an improved understanding of this process might provide a new avenue for targeting cancer cells in transit.

Domaines

Cancer
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Dates et versions

hal-02409229 , version 1 (13-12-2019)

Identifiants

  • HAL Id : hal-02409229 , version 1

Citer

Gautier Follain, David Herrmann, Sebastien Harlepp, Vincent Hyenne, Nael Osmani, et al.. Fluids and their mechanics in tumour transit: shaping metastasis. Nature Reviews Cancer, 2019. ⟨hal-02409229⟩

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