Abstract
The experimental evaluation of metastasis overly focuses on the gain of migratory and invasive properties, while disregarding the contributions of cellular plasticity, extra-cellular matrix heterogeneity, niche interactions, and tissue architecture. Traditional cell-based assays often restrict the inclusion of these processes and warrant the implementation of approaches that provide an enhanced spatiotemporal resolution of the metastatic cascade. Time lapse imaging represents such an underutilized approach in cancer biology, especially in the context of disease progression. The inclusion of time lapse microscopy and microfluidic devices in routine assays has recently discerned several nuances of the metastatic cascade. Our review emphasizes that a complete comprehension of metastasis in view of evolving ideologies necessitates (i) the use of appropriate, context-specific assays and understanding their inherent limitations; (ii) cautious derivation of inferences to avoid erroneous/overestimated clinical extrapolations; (iii) corroboration between multiple assay outputs to gauge metastatic potential; and (iv) the development of protocols with improved in situ implications. We further believe that the adoption of improved quantitative approaches in these assays can generate predictive algorithms that may expedite therapeutic strategies targeting metastasis via the development of disease relevant model systems. Such approaches could potentiate the restructuring of the cancer metastasis paradigm through an emphasis on the development of next-generation real-time assays.
Highlights
Metastasis generates a systemic disease driven by the concerted alliance of tumor cell dissociation, physical translocation, and distant colonization
These processes are further influenced by numerous physiological parameters, including the tissue stroma, architecture, and extra-cellular matrix (ECM) composition, in order to facilitate the successful establishment of a secondary disease [1,2,3,4]
Recent studies reveal a functional uncoupling of several physiological processes previously deemed crucial for successful metastasis
Summary
Metastasis generates a systemic disease driven by the concerted alliance of tumor cell dissociation, physical translocation, and distant colonization. Recent studies highlight a collective mode of dissemination, wherein the retention of several epithelial properties is well documented [1,2,3,4] These processes are further influenced by numerous physiological parameters, including the tissue stroma, architecture, and extra-cellular matrix (ECM) composition, in order to facilitate the successful establishment of a secondary disease [1,2,3,4]. In vitro functional read-o2u.2t.sFupnrcotvioindael Aassapyrseliminary assessment of the metastatic capabilities, while the variables contributing to tumor heterogeneity viz., micro-environmental milieu, tissue specific metabolic gradieanidtse,dTahbneydecxesalylm-sbitanesametdioicnasaosrafcyfhus.intRcetcoiotuuntiranelei,tliyeasreeamcoproflotsesynetdhaeaspsssheasyyssseiodilnogwciacinathcl earinnbdivopilvaotgohyomlgoaogudicgeaellsts.htaetWepsrhoisiplreeortboiueussrtolyrfeview focussaensooinkisthreeswistiadnecley, esmtemplnoeyses,dmfuignrcattiioonn,ailnavsassaioyns,caonrdrecsoploonnidziantigonto, stohraesetdo icsotirnrecltastetawgeitshocflimniecatal stasis, viz., proibmsearrvyatdioinssso(TciaabtlieoSn1, apnhdyFsiigcuarletr1a).nslocation, and colonization, we briefly discuss the molecular approaches routinely used in cancer biology (Figure 1). Circulating tumor cells overcome hydrostatic pressures and immune surveillance to extravasate and colonize distant tissues to seed micro-/macro-metastases. A list of the relevant assays employed across the metastatic cascade are listed and indicated in the schematic
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