New mechanism found on how a parasite leads to cancer
S. haematobia eggs embedded in the bladder wall - Image from the CDC Public Health Image Library.
About 200 million people across 75 of the poorest countries in the world are now infected by the blood parasite Schistosoma haematobium (S. haematobium). The infection causes severe urogenital disease, but also causes bladder cancer in a number of patients and why this occurs is not clear.
But now a group of Portuguese scientists believe they have the answer – their research shows that the parasite's eggs can make human bladder cells behave as cancerous cells. And that key to this – according to the first author of the work Mónica Botelho– are catechol oestrogens, a molecule derived from oestrogen (the sex hormone) that was found by the researchers in the eggs and is known to be highly carcinogenic (causes cancer).
The research, a collaboration of the CECA/ICETA from the University of Porto, the National Institute of Health in Porto, Portugal and the George Washington University, US could be a first step towards one day be able to identify S. haematobium infected patients at risk of bladder cancer or even prevent the cancer by targeting catechol-oestrogens. Schistosomiasis is also associated to fertility problems and the newfound molecules might hold the key to also understand this.
Schistosomiasis, despite the numbers infected, remains a neglected tropical disease that affects the world's poorest with a socioeconomically impact in the developing world only second to malaria. The disease is transmitted to humans by freshwater snails from contaminated waters, with the worms entering our blood stream to release eggs that become embedded in the bladder wall where they cause chronic inflammation and, in some patients, lead to bladder cancer.
How common is this carcinoma among parasite-infected patients is difficult to know because the most affected countries are also the world's poorest with scarce or even non-existing disease recording. Nevertheless, in Egypt, disappearance of S. haematobium saw the type of tumours associated with the infection going from being almost 80% of all diagnosed bladder cancers, to less than 27 %, suggesting that the infection leads to a significant number of cancer cases.
Botelho and colleagues have been investigating this relationship for many years, and shown already that extract from the adult worm could make animal cells acquire cancer-like characteristics and even form tumours (further proving the parasite-cancer link).
Schistosomiasis_Life_Cycle.Following the finding that Schistosomiasis' patients had higher than normal levels of oestrogens Botelho and colleagues also discovered new oestrogenic molecules released by the parasite into the host. These molecules were shown to down-regulate oestrogen receptors blocking the host's oestrogens (that act through these receptors). This, as Botelho explains "was an important clue because we know that oestrogen receptors are reduced when cancer becomes more invasive".
The new molecules were later identified as a combination of DNA and catechol oestrogen-quinones (a derivate of oestrogen). Catechol oestrogens have been linked to several types of cancer, including breast and prostate cancer, suggesting that the new molecules could be the link between schistosomiasis and bladder cancer.
The research now published follows these results looking at the effect of S. haematobium eggs (the parasite stage associated with the cancer development) on normal human bladder cells. To start Botelho and colleagues exposed the cells to extract from the eggs to find that treated cells, when compared with normal control cells, divided much more, died much less and showed signs of oxidative stress. Uncontrolled cell division and resistance to die are hallmark characteristics of cancer, and oxidative stress is known to be implicated in cancer formation.
To confirm that these changes were linked to cancer Botelho and colleagues next looked for DNA lesions. If DNA - the cell's "instruction book" - becomes damaged and is not properly repaired, it will start giving wrong "instructions", which can lead to the abnormal behaviour typical of cancer (uncontrolled cell multiplication, "immortality", etc.). And in fact, exposure to parasite's eggs was linked to a visible increase in DNA lesions in cells. The eggs were confirmed to contain the same new oestrogenic molecules found in adult worms.
Based on the new data, Botelho and colleagues are now proposing a mechanism for the Schistosomiasis-bladder cancer connection. As Botelho explains, "What we think happens is that the parasite releases oestrogen molecules into the host. These are metabolized into catechol-oestrogen quinones, which are known to have high affinity for DNA and as result form oestrogen-DNA adducts that can lead to the bladder cancer."
In fact, adducts (defined as pieces of DNA covalently bonded to a cancer-causing chemical) are known to interfere with normal cell division, increasing the chance of DNA mutations and, consequently, of cancer. The carcinogenic effect of the oestrogen–DNA adduct could then explain the link between S. haematobium infection and the carcinoma.
Botelho and colleague's work have several implications – the possibility of using the new identified oestrogenic molecules as biomarkers for bladder cancer in Schistosomiasis patients, or even as therapy targets for a start.
This is important because although at the moment it is suggested that there are about 4 cases of cancer for 100 000 Schistosomiasis-infected individuals what does not seem much, we must remember that 200 millions people are believed to be infected. And even those numbers, like the Egypt case suggests, are probably a gross underestimation. After all carcinoma of the urinary bladder is the most common malignancy in the Middle East and parts of Africa where schistosomiasis is a major problem.
Not only that but, and despite the existence of a cheap and effective drug, the disease (which is asymptomatic until very late) seems to be increasing and spreading. This is probably due to the large numbers of economical migrants from developing countries, as well as the many wars in these areas of the globe causing large displacements of people.
Another interesting potential implication for Botelho's results is the possibility that the new identified oestrogenic molecules could have a role in other cancers associated with infection and oestrogenic changes, such as cholangiocarcinoma, a liver cancer linked to infection by a parasitic liver fluke.
A question remains though - why does the parasite produce oestrogenic molecules? An option, according to the researchers, could be that the parasite uses them to reduce the density of the bladder wall (a known effect of reduced oestrogen receptors). After all S. haematobium eggs must cross the bladder mucosa to be excreted in order to survive and continue its life cycle. Another possibility is that the parasite is manipulating the host's hormonal environment to improve its own living conditions.
Part of Botelho's future work will be looking at the effect of the new oestrogenic molecules on the parasite life cycle.
More information: Botelho, M.C., et al. Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma hae- matobium: An oestrogen–DNA adducts mediated pathway? Int. J. Parasitol. (2013), dx.doi.org/10.1016… .2012.10.023
Provided by Ciencia Viva
- Portuguese scientists show Schistosoma haematobium direct link to tumours Jul 30, 2009 | not rated yet | 0
- Genetic code cracked for a devastating blood parasite Jan 18, 2012 | not rated yet | 0
- Researchers show host Mta1 gene is required for optimal survival of schistosome parasites Jun 01, 2011 | not rated yet | 0
- Sneak peek at early course of bladder infection caused by widespread, understudied parasite Nov 29, 2012 | not rated yet | 0
- Novel basis identified for tamoxifen failure Dec 04, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
13 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
The gap between life expectancy in patients with a mental illness and the general population has widened since 1985 and efforts to reduce this gap should focus on improving physical health, suggest researchers in a paper ...
Cancer 2 hours ago | not rated yet | 0
By studying the roles two proteins, thrombospondin-1 and prosaposin, play in discouraging cancer metastasis, a trans-Atlantic research team has identified a five-amino acid fragment of prosaposin that significantly reduces ...
Cancer 3 hours ago | not rated yet | 0
A novel transcriptome-based classification of colon cancer that improves the current disease stratification based on clinicopathological variables and common DNA markers is presented in a study published in PLOS Medicine this w ...
Cancer 3 hours ago | not rated yet | 0
A study of veterans at high risk for developing lung cancer shows that low-dose computed tomography (LDCT) can be highly effective in helping clinicians spot tiny lung nodules which, in a small number of patients, may indicate ...
Cancer 5 hours ago | not rated yet | 0
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
Cancer 7 hours ago | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
9 hours ago | 4 / 5 (4) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
2 hours ago | 5 / 5 (1) | 0
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
7 hours ago | 4.8 / 5 (6) | 0 |
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
3 hours ago | 5 / 5 (3) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
4 hours ago | not rated yet | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
9 hours ago | 4.8 / 5 (4) | 0 |