Many tumours can already nowadays be treated effectively – but before they have formed metastases. Once the cancer has spread into the body, in 90 percent of cases it is no longer able to be tamed. The mechanisms by which individual cells are released from a cell cluster, and manage to migrate to another location in the body via the bloodstream or lymphatic system, giving rise to a new tumour, are virtually unknown. It has not been clear until now whether all malignant cells are capable of metastasis or whether this capacity is reserved for only a certain subpopulation.
Metastatising cells carry CD36 receptors
Using a fluorescent colouring, scientists have now discovered a particular cell type in oral cancer which is capable of metastasising. These cells all generally carry receptor CD36 in their cell membrane. This protein is responsible for incorporating fatty acids into the cell. The amazing thing: when the researchers supplied CD36 to non metastasising tumour cells, they were also able to metastasise.
CD36: general metastasis marker
The researchers were able to observe this effect with melanoma cells and luminal breast cancer as well. Statistical analysis of patient samples also showed that the metastases of ovary, bladder and lung cancer depend on CD36.
“Although we have not tested all cancers, we can say that CD36 is a general marker for metastatic cells – the first marker I know of which is generally specific to metastasis. This is also suggested by study results from cooperating workgroups”, says study leader Salvador Aznar Benitah of the Stem Cell and Cancer Laboratory at the Institute for Research and Biomedicine in Barcelona. Thanks to the newly discovered marker and a matching antibody, scientists can now select metastatic cells in the laboratory and specifically examine them more closely. “We can find out how these cells are distributed in a tumour, when they leave the tumour, and where they set anchor. In addition, why it is that these cells are so fat-sensitive is something that needs to be revealed”, explains lead author Gloria Pascual.
(Palm) fat promotes metastasis
Next up, the researchers examined whether fat intake in the diet has a direct effect on metastasis. For this purpose they fed mice with high-fat diet containing 15% more fat than usual – a sort of “cafeteria diet”. The researchers then administered oral cancer cells to the animals, which under normal feeding conditions leads to about 30% of the animals develop metastases. Alongside the high-fat diet and its correlated blood lipid increase, 80% of the mice developed many more and larger metastases.
In the next step, the researchers looked at the effect of palmitic acid more precisely. This vegetable fatty acid is the main component of palm oil and occurs in smaller proportions in coconut and other oils, but is mainly found in processed foods. The researchers treated the oral tumours for two days with palmitic acid and then injected it into normally fed mice. The result: metastasis incidence rose from 50 percent to 100 percent – all mice developed CD36-dependent metastases.
“In mice with human tumour cells, a direct link seems to exist between fat intake and the ability to form metastases via CD36”, according to Benitah, who adds: “We need more studies to clarify the relationship between diet and metastases, mainly because the consumption of saturated fat and sugar in industrialised countries has increased dramatically. Fat is indeed essential for many body functions, although its uncontrolled consumption can however definitely influence our health, as already demonstrated in colon cancer, and by us here for example in relation to metastases”.
At the moment, the scientists led by Benitah are testing how different fats in our food impact upon the ability of cancer cells to metastasise. “Prior to the publication of the results, I’m not able to reveal too much. Just this: We have observed very interesting differences! Some fatty acids reinforce the metastasis, others do not – and some even appear to protect against metastasis,” says Benitah. The scientist is now trying to more consciously abstain from palm oil. “It’s not an easy job, since many processed products from the grocery store contain palm oil”.
CD36 as a therapeutic target against metastasis
The metastasis of cancer cells is not only able to be reduced through abstinence from palmitic acid – the scientists were also successful by using an antibody. By blocking the CD36 fat receptor, they were able to stop metastasis. This worked in both immunosuppressed mice and in mice with an intact immune system. The CD36 antibody prevented not only the formation of CD36-dependent metastases in animal studies, it also performed a good service in mice whose tumours had already spread: in 20% of the animals, the metastases completely receded. In the others the CD36 antibody reduced the number of metastases and their size by 80 to 90%.
Hardly any side effects in animal experiments
A look at both results and side effects from animal experiments gives ground for optimism: the metastasis-reducing antibody treatment was well tolerated by the animals. Later autopsies, blood and tissue analysis showed no intolerable side effects from the treatment. The scientists have already applied for a patent protection for their discovery. Therapeutic antibodies are being developed in cooperation with an English company. Should developments run according to plan, the antibody could be available for use on cancer patients in five to ten years.