There are many proteins on the outside of our body cells, a thousand different types
If B cells of the immune system no longer have the protein CD37 on their outside, they can derail and thus form blood cancer. CD37 inhibits fat absorption in healthy cells. If this protein is missing, a tumor cell absorbs much more fat and therefore grows faster. This is apparent from a publication by Annemiek van Spriel’s team in Nature Communications. The finding provides a stepping stone to new therapy for B-cell lymphoma.
There are many proteins on the outside of our body cells, a thousand different types. Those proteins are like cousins: they fish tasty snacks into the cell, maintain contact with the neighbors and ensure communication with cells located further away. An important group of these control cousins are the so-called tetraspanins. These proteins mainly occur together with other proteins on the same cell. In this way they form small islands, where they arrange all kinds of things.
‘We still know little about tetraspanins, but we are seeing more and more evidence that they play a role in cancer,’ explains Annemiek van Spriel, professor of Experimental Immunology at Radboudumc. She has been researching tetraspanins for almost twenty years and is unraveling their functions step by step. ‘We use models in which we switch off a specific tetraspanin and see what happens. For example, a few years ago we discovered that certain immune cells, called B cells, derail when they no longer contain the tetraspanin CD37. They then turn into tumor cells.’
Vette hap
The mechanism behind this derailment remained unclear for a long time, but now Van Spriel and her team have worked out exactly what is going on. ‘CD37 inhibits the absorption of fat in healthy cells via special fatty acid channels. If CD37 is missing, a cell can therefore absorb much more fat. Fat is the basis for all kinds of building materials and contains a lot of energy, much more than sugar. A cell that absorbs a lot of fat can therefore grow and divide faster than a normal cell. And that’s exactly what tumor cells like to do. Due to the lack of CD37, a healthy cell therefore changes more quickly into a tumor cell.’
When B cells derail, blood cancer of the B cells, also known as B cell lymphoma, develops. The most common and aggressive form is called DLBCL (diffuse large B-cell lymphoma), a disease with 1500 diagnoses per year in the Netherlands. Van Spriel looked at tumor material from these patients: ‘We discovered that half of them had no CD37 on the outside of the tumor cells. That turned out to be exactly the group that has less good prospects: these patients respond worse to the current standard therapy, a combination of chemotherapy and immunotherapy, and they live less long.’
Switch
Does this discovery offer leads for new therapy? ‘There are substances that bind specifically to CD37. If you administer them, they ensure that tumor cells die’, explains Van Spriel. ‘Together with the company Genmab, we are investigating new forms of immunotherapy aimed at CD37. In addition, you can achieve more effect with combination therapies, such as chemotherapy or radioactive radiation. This therapy is only suitable if tumor cells still have CD37.’
But it is precisely the tumor cells without CD37 that give a worse outlook for patients. ‘We are investigating alternative options for this group,’ says Van Spriel. ‘Currently, several preclinical studies are underway in the United States in models of blood cancer and other cancers, testing new drugs that block fat channels. These substances, as it were, take over the role of the missing CD37 and inhibit tumor growth. It’s great that fundamental research into proteins on the cell contributes to the development of new options for therapy in patients.’
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