A specific protein called CD36 has been identified on cancer cells which have the ability to metastasize.
CD36, found in the cell membranes of tumor cells, is responsible for taking up fatty acids. This unique CD36 activity and dependence on fatty acids distinguishes metastasis-initiating cells from other tumor cells.
The team of scientists, headed by Professor Salvador Aznar Benitah, of the Institute for Research in Barcelona, found CD36 was present on metastatic cancer cells from patients with a range of different tumors including oral tumors, melanoma skin cancer, ovarian, bladder, lung and breast cancer.
Marker Specific To Metastasis
Cancer is most deadly when it has begun to spread as successful treatment is much more difficult. Scientists around the globe are therefore trying to understand how the process occurs and develop new ways to stop it.
To confirm its essential role in cancer spread, Professor Benitah’s team added CD36 to non-metastatic cancer cells which then caused the cells to become metastatic.
“Although we have not yet tested this in all tumor types, we can state that CD36 is a general marker of metastatic cells, the first I know of that is generally specific to metastasis,” says Professor Benitah. “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."
The researchers next looked at the role of fat intake on cancer spread. They provided mice with a high fat diet then injected them with a type of human oral cancer. The high fat diet caused 50% more mice to have larger and more frequent metastases.
They went on to test a specific saturated fatty acid called palmitic acid - a major component of animal and vegetable fats and present at high levels in palm oil which is used in many house hold products from peanut butter and processed food to toothpaste.
The researchers treated human oral tumors with palmitic acid for two days then injected them into mice fed a standard diet. The team observed that all the mice with CD36 developed cancer spread compared to only half when not treated with palmitic acid.
“In mice inoculated with human tumor 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, above all because industrialised countries are registering an alarming increase in the consumption of saturated fats and sugar,” warns Professor 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."
CD36 Blocking Antibodies
Using mice with human oral cancer, the researchers were next able to show that blocking CD36 completely prevented metastasis.
In mice with cancer cells that had already metastasised, CD36 blocking antibodies led to the complete removal of metastases in 20% of the mice, whilst in the others it caused a dramatic reduction of 80-90% of metastases and reduced the size. Importantly, this was all achieved with no serious side effects.
The researchers are now developing new antibody-based therapeutics against CD36 that could potentially be suitable to treat a range of cancers in patients in the future.
Gloria Pascual, Alexandra Avgustinova, Stefania Mejetta, Mercè 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; DOI: 10.1038/nature20791
Image: Anne Weston, LRI, CRUK, Wellcome Images. False-coloured scanning electron micrograph of a single prostate cancer cell grown in culture.