A study headed by Salvador Aznar Benitah, ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona), and published 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.”
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.
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.
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).
More information at IRB Barcelona website.