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Switching Homes: How Cancer Moves to Bone.

ABSTRACT: Bone metastases (BM) are a very common complication of the most prevalent human cancers. BM are extremely painful and may be life-threatening when associated with hypercalcaemia. BM can lead to kidney failure and cardiac arrhythmias and arrest, but why and how do cancer cells decide to "switch homes" and move to bone? In this review, we will present what answers science has provided so far, with focus on the molecular mechanisms and cellular aspects of well-established findings, such as the concept of "vicious cycle" and "osteolytic" vs. "osteosclerotic" bone metastases; as well as on novel concepts, such as cellular dormancy and extracellular vesicles. At the molecular level, we will focus on hypoxia-associated factors and angiogenesis, the Wnt pathway, parathyroid hormone-related peptide (PTHrP) and chemokines. At the supramolecular/cellular level, we will discuss tumour dormancy, id est the mechanisms through which a small contingent of tumour cells coming from the primary site may be kept dormant in the endosteal niche for many years. Finally, we will present a potential role for the multimolecular mediators known as extracellular vesicles in determining bone-tropism and establishing a premetastatic niche by influencing the bone microenvironment.

SUBMITTER: Ponzetti M

PROVIDER: S-EPMC7313057 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Switching Homes: How Cancer Moves to Bone.

Ponzetti Marco M Rucci Nadia N

International journal of molecular sciences 20200609 11

Bone metastases (BM) are a very common complication of the most prevalent human cancers. BM are extremely painful and may be life-threatening when associated with hypercalcaemia. BM can lead to kidney failure and cardiac arrhythmias and arrest, but why and how do cancer cells decide to "switch homes" and move to bone? In this review, we will present what answers science has provided so far, with focus on the molecular mechanisms and cellular aspects of well-established findings, such as the conc ...[more]

PMID: 32527062

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Project description:BackgroundThis paper provides a summary of a Keynote lecture delivered at the 2009 Australasian Podiatry Conference. The aim of the paper is to review recent research that has adopted dynamic cadaver and invasive kinematics research approaches to better understand foot and ankle kinematics during gait. It is not intended to systematically cover all literature related to foot and ankle kinematics (such as research using surface mounted markers). Since the paper is based on a keynote presentation its focuses on the authors own experiences and work in the main, drawing on the work of others where appropriateMethodsTwo approaches to the problem of accessing and measuring the kinematics of individual anatomical structures in the foot have been taken, (i) static and dynamic cadaver models, and (ii) invasive in-vivo research. Cadaver models offer the advantage that there is complete access to all the tissues of the foot, but the cadaver must be manipulated and loaded in a manner which replicates how the foot would have performed when in-vivo. The key value of invasive in-vivo foot kinematics research is the validity of the description of foot kinematics, but the key difficulty is how generalisable this data is to the wider population.ResultsThrough these techniques a great deal has been learnt. We better understand the valuable contribution mid and forefoot joints make to foot biomechanics, and how the ankle and subtalar joints can have almost comparable roles. Variation between people in foot kinematics is high and normal. This includes variation in how specific joints move and how combinations of joints move. The foot continues to demonstrate its flexibility in enabling us to get from A to B via a large number of different kinematic solutions.ConclusionRather than continue to apply a poorly founded model of foot type whose basis is to make all feet meet criteria for the mechanical 'ideal' or 'normal' foot, we should embrace variation between feet and identify it as an opportunity to develop patient-specific clinical models of foot function.

Project description:Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure. Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use, from maximum likelihood and parsimony to distance-based principles, and in a Bayesian context. Their basic components are rearrangement moves that specify all possible ways of generating alternative phylogenies from a given one, and whose fundamental property is to be able to transform, by repeated application, any phylogeny into any other phylogeny. Despite their long tradition in tree-based phylogenetics, very little research has gone into studying similar rearrangement operations for phylogenetic network-that is, phylogenies explicitly representing scenarios that include reticulate events such as hybridization, horizontal gene transfer, population admixture, and recombination. To fill this gap, we propose "horizontal" moves that ensure that every network of a certain complexity can be reached from any other network of the same complexity, and "vertical" moves that ensure reachability between networks of different complexities. When applied to phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best-known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted subtree pruning and regrafting. Besides a number of reachability results-separating the contributions of horizontal and vertical moves-we prove that rNNI moves are local versions of rSPR moves, and provide bounds on the sizes of the rNNI neighborhoods. The paper focuses on the most biologically meaningful versions of phylogenetic networks, where edges are oriented and reticulation events clearly identified. Moreover, our rearrangement moves are robust to the fact that networks with higher complexity usually allow a better fit with the data. Our goal is to provide a solid basis for practical phylogenetic network reconstruction.

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Switching Homes: How Cancer Moves to Bone.

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Switching Homes: How Cancer Moves to Bone.

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