Nav: Home

Tumor cells are dependent on fat to start metastasis

December 07, 2016

A study headed by Salvador Aznar Benitah, ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona), and published today in Nature identifies metastasis-initiating cells through a specific marker, namely the protein CD36. This protein, which is found in the membranes of tumour cells, is responsible for taking up fatty acids. CD36 activity and dependence on lipid (fat) metabolism distinguish metastasis-initiating cells from other tumour cells.

The researchers discovered the metastatic CD36+ cells in samples from patients with oral cancer with different degrees of aggressiveness, provided as part of a collaboration with the Hospital Vall d'Hebrón de Barcelona. In the mouth tumours analysed, very few cells were found to have metastasis-initiating capacity. The addition of CD36 expression to tumours that did not cause metastasis made them become metastatic.

Furthermore, the researchers have demonstrated that the effect exerted by CD36 on metastasis is the same for melanoma cells and luminal breast cancer cells. Likewise, statistical analyses of samples from patients reveal that the metastasis of ovarian, bladder and lung cancer are also dependent on CD36.

"Although we have not yet tested this in all tumour types, we can state that CD36 is a general marker of metastatic cells, the first marker I know of that is generally specific to metastasis," says Salvador Aznar Benitah, head of the Stem Cell and Cancer Lab at IRB Barcelona. "We can now obtain metastatic cells in the laboratory. This will allow us to trace them and to study, for example, their distribution in the tumour, where they anchor when they leave it, or why they are so sensitive to fat, among other questions," adds the first author of the study Gloria Pascual.

Dr. Aznar-Benitah pointed that "We expect this study to have a big impact on the scientific community and to further advances in metastasis research, and we hope to be able to validate the potential of CD36 as an anti-metastasis treatment. Things like this don't happen every day."

Fat and metastasis

Given the involvement of lipid metabolism in metastasis and the function of CD36 in this process, the next logical question for the researchers was: does fat intake have a direct effect on metastasis? The researchers provided mice with a high-fat diet (15% more fat that normal, equivalent to what a so-called "cafeteria diet"). They then inoculated them with a type of oral cancer, which in standard dietary conditions would lead to 30% of the animals developing metastasis. Strikingly, under the high-fat diet and thus with a greater amount of lipids in blood, around 80% of the mice developed many more and larger metastases.

They also tested the effect of a specific fatty acid, palmitic acid, on metastasis. This plant-derived fatty acid is the main component of palm oil, and in lower proportions, of coconut and other oils, and is used in many kinds of processed food. The researchers treated the oral tumours with palmitic acid for two days and then injected them into mice on a standard diet,.An increase from 50 to 100% was observed in the frequency of the metastatic tumour. That is to say, all the mice developed metastasis in a CD36-dependent manner.

"In mice inoculated with human tumour cells, there appears to be a direct link between fat intake and an increase in metastatic potential through CD36. More studies are needed to unravel this intriguing relationship between diet and metastasis, above all because industrialised countries are registering an alarming increase in the consumption of saturated fats and sugar," warns Aznar Benitah. "Fat is necessary for the function of the body, but uncontrolled intake can have an effect on health, as already shown for some tumours such as colon cancer, and in metastasis, as we demonstrate here," explains the researcher.

Is CD36 a therapeutic target for metastasis?

The study demonstrates the anti-metastatic effect of blocking the CD36 protein, both in immunodepressed mice and in mice with intact immune systems. Figures were similar for all tests. The inhibition of CD36 when the animals were inoculated with the tumour cells completely eliminated their metastatic potential. In addition, the administration of CD36-blocking antibodies to mice with already established metastases led to total removal of the metastases in 20% of the animals, while for the others it brought about a dramatic reduction of 80-90% in the number of metastatic foci and their size.

The mice tolerated the treatment in the therapeutic window required to achieve an anti-metastasis effect and no intolerable side-effects were observed in autopsies, and blood and tissue analyses.

IRB Barcelona has applied for IP protection of the results, and the researchers are working with MRC Technology in the UK to co-develop new antibody-based therapeutics against CD36 that are suitable for treatment of patients in a range of cancers. If the development of the novel therapeutic was successful, a new product could be available in 5-10 years.
-end-
The study has been possible thanks to the collaboration of the Service of Oral and Maxillofacial Surgery, the Service of Pathology Anatomy and the biobank of the Hospital Vall d'Hebrón de Barcelona, with the participation of Coro Bescós and Juan Antonio Hueto from the Vall d'Hebron Institut de Recerca (VHIR). The study is thus the result of collaboration between basic and clinical research and it aims to transform research results into useful treatments for patients.

This work has been supported by the Fundació La Marató de TV3, two project grants from the World Wide Cancer Research of the UK, and Fundación Botín and Banco Santander, through Santander Universidades. Furthermore, the laboratory is supported by funding from the European Research Council, the Ministry of Science and Innovation, and the Generalitat de Catalunya (Government of Catalonia).

Reference article:

Gloria Pascual, Alexandra Avgustinova, Stefania Mejetta, Mercé Martín, Andrés Castellanos, Camille Stephan-Otto Attolini, Antoni Berenguer, Neus Prats, Agustí Toll, Juan Antonio Hueto, Coro Bescós, Luciano Di Croce & Salvador Aznar Benitah
Targeting metastasis-initiating cells through the fatty acid receptor CD36
Nature (2016) 10.1038/nature20791

Institute for Research in Biomedicine (IRB Barcelona)

Related Fatty Acids Articles:

Efficiently producing fatty acids and biofuels from glucose
Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.
Omega-3 fatty acids tied to fewer childhood asthma symptoms
A six-month study of children from Baltimore City by Johns Hopkins Medicine researchers has added to evidence that having more omega-3 fatty acids in the diet results in fewer asthma symptoms triggered by indoor air pollution.
Could omega-3 fatty acids help prevent miscarriages?
A new study in mice reveals that omega-3s, a type of fat found in fish oil, reduces fetal and neonatal deaths, suggesting they could prevent some miscarriages in women.
Researchers reveal prostate tumors 'fed' by fatty acids
An international multidisciplinary study initiated by Melbourne scientists has shown a link between prostate cancer and the uptake of fatty acids by cancer cells.
A hidden route for fatty acids can make cancers resistant to therapy
Researchers from the lab of Prof. Sarah-Maria Fendt at the VIB-KU Leuven Center for Cancer Biology now demonstrate that certain tumor cells use an alternative -- previously unexplored -- pathway to produce fatty acids.
Sunscreen and cosmetics compound may harm coral by altering fatty acids
Although sunscreen is critical for preventing sunburns and skin cancer, some of its ingredients are not so beneficial to ocean-dwelling creatures.
New Parkinson's disease drug target revealed through study of fatty acids
A new study led by investigators from Brigham and Women's Hospital and Harvard Medical School has provided insights into the role of fatty acids and suggests that inhibiting a specific enzyme can protect against neurotoxicity.
Omega 3 fatty acids found in seafood linked to healthy aging
Higher blood levels of omega 3 fatty acids found in seafood are associated with a higher likelihood of healthy ageing among older adults, finds a US study published by The BMJ today.
Fatty acids can slow down an overheated immune system
The STING protein is normally an important part of our immune system, but in some autoimmune diseases it is itself the source of the disease.
International team makes rare discovery of new fatty acids
Decades after scientists discovered hundreds of different fatty acids in vegetable oils, two that had managed to elude detection have finally revealed themselves to a team led by the University of Nebraska-Lincoln and Huazhong Agricultural University in China.
More Fatty Acids News and Fatty Acids Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#542 Climate Doomsday
Have you heard? Climate change. We did it. And it's bad. It's going to be worse. We are already suffering the effects of it in many ways. How should we TALK about the dangers we are facing, though? Should we get people good and scared? Or give them hope? Or both? Host Bethany Brookshire talks with David Wallace-Wells and Sheril Kirschenbaum to find out. This episode is hosted by Bethany Brookshire, science writer from Science News. Related links: Why Climate Disasters Might Not Boost Public Engagement on Climate Change on The New York Times by Andrew Revkin The other kind...
Now Playing: Radiolab

Breaking Bongo
Deep fake videos have the potential to make it impossible to sort fact from fiction. And some have argued that this blackhole of doubt will eventually send truth itself into a death spiral. But a series of recent events in the small African nation of Gabon suggest it's already happening.  Today, we follow a ragtag group of freedom fighters as they troll Gabon's president - Ali Bongo - from afar. Using tweets, videos and the uncertainty they can carry, these insurgents test the limits of using truth to create political change and, confusingly, force us to ask: Can fake news be used for good? This episode was reported and produced by Simon Adler. Support Radiolab today at Radiolab.org/donate.