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PLOS Biology roundup

This week’s PLOS Biology roundup features three articles, two of which are published with an accompanying synopsis. Synopses are designed to summarise the main findings of an article in a more accessible form — from our article-level metrics we know they’re popular with our readers as a way of introducing more complex research prior to reading the full article.

Does stress contribute to metastasis?

Few diagnoses scare a woman more than a breast cancer diagnosis. Although overall survival rates have improved, primarily due to earlier detection and more effective treatments, the prognosis for breast cancer that metastasizes to other areas of the body remains poor, with bone metastases accounting for some 70% of deaths.

Researchers have long suspected that fear of recurrence and the emotional toll of living with breast cancer can actually hasten the spread of disease and cut short a woman’s life. Now a new study published last week in PLOS Biology shows how stress lays the groundwork for bone metastasis by providing a favorable environment for rogue breast cancer cells.

Working in a mouse model of breast cancer, the researchers, led by Florent Elefteriou, show that activating the sympathetic nervous system — which produces the fight-or-flight response to stress— creates changes in bone tissue that allows breast cancer cells to invade and proliferate. They also show that a beta blocker (propranolol) that inhibits signals from the sympathetic nervous system and is used to treat hypertension and anxiety prevented breast cancer cell lesions in bones. This suggests that beta blockers might prove a promising therapy to test in breast cancer patients. It also suggests that physicians should help patients find strategies to alleviate the stress of coping with their disease.

Losing connections — it’s all part of growing up

In a recent research article, Stephen Turney and Jeff Lichtman, investigated the multiple synaptic connections that are made between neurons and their target cells early on in mammalian development. Many of these connections subsequently disappear through a process of ‘synaptic pruning’ that takes place once mammals are born. Exactly what causes this pruning is not well understood, though it’s thought that it may be to shape the nervous system appropriately. Research elsewhere suggest that phenomena such as synaesthesia in adults (‘seeing’ sounds as colours, for instance) might arise from a cross-activation caused by a failure of the pruning process.

Dynamic Remodeling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex
Dynamic Remodeling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex. Image credit: Lee W-CA et al. (2006) PLoS Biol 4(2): e29. doi:10.1371/journal.pbio.0040029

In order to explore what might be happening at this early stage, the researchers studied the connections between motor neuron axons (nerve cells) and their target muscle cells in mice one week after birth, at a stage when there are still multiple connections. They found that the reduction in the number of synaptic connections followed as nerve cells competed to maintain their connection to the same target cell. If they removed a competitor nerve cell, by laser microsurgery, another that would otherwise have been eliminated went on not only to survive, but to take over the vacated site. Reversing the outcome of synapse elimination in this manner gave the researchers further insight into the intriguing nature of the synaptic rearrangements that go on as the nervous system develops.

In an accompanying synopsis, Richard Robinson explains the researchers’ approach in more detail.

Molecule movements: how the ECM takes control

The interstitial spaces between cells in animal and plant tissue are filled by an extracellular matrix, or ECM, a gelatinous network composed largely of polysaccharides and glycoproteins. The ECM is an extensive and complex structure and performs many vital functions, among them providing structural support to cells and facilitating cell-cell communication by binding and transporting  numerous proteins, including cytokines, morphogens and growth factors.  Understanding the way in which cells and proteins move across the ECM provides new insights into the complex dynamics that drive cell communication in development and disease.

In a  paper recently published in PLOS Biology, Laurence Duchesne, David Fernig and colleagues investigate the movement of an important growth factor, called fibroblast growth factor 2 (FGF2), within the ECM using two imaging techniques to locate and track this molecule’s movements. The researchers knew that the polysaccharide heparin sulfate (HS) plays a crucial role in regulating how particular proteins, such as FGFs, are bound and transported in the ECM. So to investigate the nature of growth factor binding by HS in the ECM, these authors  labeled FGF2 proteins with gold nanoparticles, which allowed them to use both electron microscopy and a new photothermal heterodyne imaging technique to track FGF2’s movements.

Diffusion of an individual FGF2 (from Figure 5, Duchesne L, et al.)
Image credit: Diffusion of an individual FGF2 (from Figure 5, Duchesne et al. (2012) Transport of Fibroblast Growth Factor 2 in the Pericellular Matrix Is Controlled by the Spatial Distribution of Its Binding Sites in Heparan Sulfate. PLoS Biol 10(7): e1001361. doi:10.1371/journal.pbio.1001361

They discovered that the majority of FGF2 molecules spend most of their time either immobile or confined to the ECM; however, they are not trapped here and can escape by simple diffusion, which can be slow, fast or directed. From their findings the team concluded that FGF2 can move within the ECM by translocating from one HS-binding site to another, and that the binding sites on HS chains form non-random, heterogeneous networks, which promote FGF2 confinement or translocation depending on their spatial organisation.

In an accompanying synopsis, Richard Robinson explains this research in more detail and describes the interesting imaging techniques the authors used in this study.


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