Fats may be key in the fight against metastasis
<p>Scientists at IRB Barcelona have identified a cellular protein responsible for initiating and promoting metastasis in some types of tumors</p>
A study led by ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona) Salvador Aznar Benitah points to the protein CD36, which absorbs fats from the cell membrane, as a decisive factor in tumor cells becoming metastatic.
The study, published in Nature, analyzed samples from patients with oral carcinoma and observed that tumors that don't have the CD36 protein don’t metastasize. Plus, adding CD36 to tumors that don’t lead to metastasis causes them to metastasize and inhibiting the protein drastically reduces metastases already established.
The researchers have proven that the effects of CD36 on metastasis are the same in melanoma and luminal breast cancer. “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 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.
After seeing how fat metabolism is involved, researchers wanted to find out whether fat intake has a direct effect on metastasis. They inoculated mice with a type of oral cancer and what they saw was that 80% of the mice with a high-fat diet (15% above average) developed metastasis. However only 30% of mice with a normal diet did. There seems to be a direct link between fat intake and increased potential for metastasis, at least in mice inoculated with human tumor cells.
CD36, therapeutic target for metastasis?
The study demonstrates that blocking the CD36 protein has anti-metastatic effects, both in immunodepressed mice and in those with healthy immune systems. The figures were similar on all the tests. Additionally, administering CD36-blocking antibodies to mice with metastasis led to total removal of the metastases in 20% of mice and a drastic reduction in the number of foci and size.
Treatment with antibodies seems promising and, moreover, is well-tolerated by mice, which showed no intolerable side effects in autopsies. IRB Barcelona is co-developing CD36 antibodies with MRC Technology (United Kingdom), which may potentially be available to treat patients within 5 to 10 years if all goes well.
- 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): Doi: 10.1038/nature20791