Researchers at Hospital del Mar detect that low levels of a protein warn that the tumor is going to spread
The finding opens the door to testing lipid-inhibiting treatments
researchers of the Hospital del Mar Institute for Medical Research (IMIM) have discovered a marker to know when a type of skin cancer prepares to provoke metastasis.
The research, published by the journal ‘Life Science Alliance’has revealed that low levels of a protein, dyskerin, in the squamous cell carcinoma they indicate that they are preparing to initiate migration to other organs and thus cause the spread of the tumor to other areas of the body.
Researchers have seen how tumor cells prepare to migrate by changing their metabolism to be able to consume lipidsthat is to say, cholesterol moleculeswhich opens the door to study ways to block this process and prevent tumor metastasis.
The study’s principal investigator Immaculate Hernandez-Muñoz explained that when the cells that form cutaneous squamous cell carcinoma tumors prepare to migrate to the lymph nodes and cause metastasis in other organs, they stop consuming glucose to survive using glucose molecules. LDL cholesterol, the so-called ‘bad cholesterol’.
The work, which has been led by doctors from the Dermatological Inflammatory and Neoplastic Diseases Research Group of the Hospital del Mar Medical Research Institute, may open the way for test treatments with inhibitors of metabolism of lipids in these cells to prevent metastasis.
74,000 annual cases in Spain
Hernández-Muñoz recalled that every year 74,000 new cases are diagnosed in Spain non-melanoma skin cancer, a group that includes squamous cell carcinoma, the second most frequent. The risk of suffering it throughout his life ranges between 7 and 11% and its incidence has doubled in the last thirty years. In the case of squamous cell carcinoma, about 4% of tumors cause metastasis and so far there is no tool to anticipate.
Now, however, this research makes it possible to have a marker that indicates which of them are about to start migrating towards the lymph nodes to reach other organs. The researchers have been able to confirm the role of the dyskerin protein in this process from samples of a hundred primary tumors of patients with squamous cell carcinoma.
In those that metastasized, they verified with in vitro tests how certain non-coding RNA particles stopped expressing themselves and how dyskerin levels dropped, which is the protein that helps to stabilize them, that is, indicating that the tumor cells were preparing to migrate.
“It is a mechanism that can explain metastasis, but not only that, but also be a marker of the moment in which the tumor cell is preparing to migrate and start this process”, summarized Hernández-Muñoz, who has detailed that the decrease in Dyskerin levels induce a change in the metabolism of tumor cells, which go from consuming glucose to feeding on lipids, specifically bad LDL cholesterol molecules.
“This allows them to survive migrating to the lymph nodes and, from there, to other organs where they proliferate. The change is only temporary and they recover their original characteristics when they complete the entire process,” said the doctor. The scientists were able to verify with lipid metabolism indicators that this marker was present in patients with the worst prognosis.
According to Hernández-Muñoz, the study “provides us with a good model to understand how the spread of tumor cells occurs in the early stages of the tumor and opens the door to study whether people with higher levels of LDL cholesterol also have more risk of metastasis”.
The work has also verified how the treatment of the affected cells with statins, which are used to combat high levels of bad cholesterol, allows lipid metabolism to remit and prevents the initiation of the metastasis process.
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In turn, the researchers verified how this mechanism of change in cell metabolism also occurs in other types of tumors.
The Proteomics Unit of the Center for Genomic Regulation of Barcelona (CRG) has also participated in this research, funded by the Carlos III Health Institute (ISCIII).