Money doesn't grow on trees - or does it?

A recent paper published in nature communications has given evidence that Eucalyptus trees may be capable of absorbing deposits of gold from within the earth. At a time when new gold discoveries have fallen dramatically, could this be an answer to finding them?

New discoveries of gold have fallen by 45% in the last 10 years. A large amount of gold may be found deeper within the earth beneath sediments, but locating these deposits has proven incredibly difficult. One new technique that is currently in development is called biogeochemistry, which is essentially the use of biological systems (for example plants) to determine which minerals are present in the soil they grow in, through observing the concentrations of minerals which can be found in the plants themselves.

However, there are a number of problems with using this type of data, chief amongst which is the fact that gold concentrations within plants is usually incredibly low, with no unequivocal evidence suggesting that the concentration of gold in plants has any correlation to the amount of gold in the soil in which they grow. It was therefore the aim of this research to provide more solid evidence for this theory.

To do this, researchers observed the activity of Eucalyptus trees which were known to be growing above a gold deposit, buried beneath a thick layer of other sedimentary minerals.

Whilst it has previously been shown that gold particles are present around the soil of Eucalyptus trees, this research, with the use of the Australian synchrotron (a machine which uses X-rays to view matter in vivid detail) was able to provide evidence for the presence of tiny amounts of gold in the leaves, twigs and bark too, proving that the trees were actually absorbing this material through their roots buried deep beneath the earth.

This could be an important discovery in the mining of precious minerals, and even those that aren’t so precious. Normally, to find a deposit of ore, extensive exploratory mining would have to take place which would usually result in a dead end. This is both expensive and invasive to the environment that sits on top of the ore. However, if this new method of detection could be developed more extensively, all that would be required to locate what we were looking for would be a sample of leaves or twigs from the vegetation in the area. These samples would then be able to tell us exactly what was within the soil, and whether more extensive mining should take place.

What do you think about this new discovery? Can you imagine being able to pop into your back garden one day and being able to tell exactly what was in the soil by looking at just one leaf?

Comment below with your thoughts and questions and don’t forget to +1 and reshare if you enjoyed this article. 

Is a tumours micro-environment a source of innate resistance to anticancer drugs?

The RAF-MEK-ERK pathway is often mutated in a number of cancers, causing signals for cell proliferation and survival to be relentlessly activated. Various inhibitors of certain components in this pathway have been developed, but with little efficiency. It is believed that the micro-environment of a tumour can confer a level of resistance to some cancer therapies through the secretion of HGF, a growth factor produced by stromal cells.

Each new development of a treatment against cancer is met with difficulties. This study by Straussman et al focuses on the RAF-MEK-ERK pathway. This is a pathway through which extracellular signals are transduced into intracellular signals, through interaction with extracellular receptors. These signals cause the expression of transcription factors which regulate the synthesis of genes required for cell survival and proliferation, key genes when considering the formation of a cancer.

Previous research has targeted the RAS protein, a component of the RAF-MEK-ERK pathway, with unsuccessful results. This has led to research directed at the kinases downstream from RAS. It is one of these downstream kinases investigated by Straussman et al, in the form of RAF and its potential inhibitors.

RAF inhibitors (RAFis) work by interfering with the RAF protein in the RAF-MEK-ERK pathway, preventing this pathway from transducing the signals for increased proliferation. It has previously been seen that inhibiting the mutated RAF reduces cancerous growth. However, these types of responses are almost always followed by a re-emergence of that tumour, brought on through the formation of resistance. Here it is suggested that the tumour microenvironment may be conferring that resistance through the secretion of soluble factors.

Whilst the role of the microenvironment in growth and metastasis is well documented, only recent research has suggested its function in drug resistance. In order to test the microenvironments role in tumour drug resistance, Straussman et al began by developing a co-culture system. In this co-culture system, GFP–labelled tumour cells were cultured alongside stromal cells to assess modulation of drug sensitivity. This was quantified by measuring how levels of GFP changed over a set period of time. This test resulted in the observation that, when this co-culture system was exposed to RAFis, those RAFis were frequently rendered ineffective when cultured alongside stromal cells.

Strausman et al then investigated the effect of one RAFi in particular (PLX4720). To do this they tested the ability of stromal cell lines to provide 7 mutant BRAF (V600E) melanoma cell lines with resistance to the anticancer drug. This resulted in six out of the seven developing resistance to PLX4720.

It was therefore concluded that stromal cells can render certain anticancer drugs ineffective.  Straussman et al confirmed that soluble factors secreted from stromal cells were responsible for the formation of resistant tumour cells. This conformation was important, as it allowed Straussman et al to identify the exact resistance causing factor. To do this they conducted an antibody-array based analysis of a large number of secreted factors. This allowed them to compare the conditioned medium obtained from the previous 6 stromal cell lines that developed resistance to PLX4720, with stromal cell lines that had not exhibited any sign of rescue activity.

From this, HGF, a growth factor that plays a role in activating the receptor tyrosine kinase MET, was identified as the source of rescue. HGF is capable of restarting this pathway through activating MEK, bypassing the RAF component of this pathway.  Straussman et al then confirmed the presence of HGF in a number of patients being treated with a RAFi, as well as confirming the phosphorylation, and therefore activation of MET (See Figure).

In these studies it is also predicted that the presence of stromal HGF in patients is a form of innate resistance, with patients capable of producing HGF showing a much poorer response to treatment than those unable to produce it.

However, further evidence was required to fully confirm that the presence of HGF was the cause of resistance. To collect this evidence, Strausmann et al tested whether recombinant HGF was capable of inducing resistance upon tumour cells, whilst simultaneously testing whether HGF-neutralising antibodies blocked resistance to PLX4720. This confirmed that HGF was indeed capable of producing the resistant phenotype.

Could these results have a clinical impact on the treatment of cancer?

These results are important clinically in defining why certain cancer treatments aren’t always effective, as well as identifying where research should be taken to combat this resistance. This paper can be compared to those investigating sorafenib, a molecular inhibitor of a number of protein kinases which has been approved in the treatment of kidney and liver cancer.

Future developments in this field should focus on whether the formation of resistance can be blocked through inhibition of HGF, as well as identifying a time scale on how long stromal cells take to confer resistance to this treatment. If this time scale can be determined, a treatment could be developed which involves combining therapies at specific times to amplify their effectiveness. It may also be important to investigate further whether other RAFis are deemed ineffective by HGF, which could make generating second generation inhibitors important. However, it may be more prudent to investigate whether the activation of MEK, ERK or MET can be inhibited. This would have the same effect, but because inhibition would be taking place further along the pathway, there is less likelihood that resistance will form.

As mentioned by the authors, further research should also take place into investigating whether this type of resistance has a role against other anti-cancer drugs, as this may give us crucial information in combating against them.

What do you think about this research? Comment below with your thoughts and questions and don't forget to +1 if you enjoyed this article.