Metastasis-Guiding Marker Discovered in Skin Cancer Cells
Targeting LDL levels and specific proteins in tumor cells may help monitor and prevent them from metastasizing
Cells that form cutaneous squamous cell carcinoma tumors prepare themselves to migrate to the lymph nodes to metastasize other organs so that they can survive this process.
According to a study led by researchers from the Inflammatory and Neoplastic Dermatological Diseases Research Group at the IMIM-Hospital del Mar Medical Research Institute, published in the journal Life Science Alliance, these cells stop consuming glucose and survive using cholesterol molecules. This new marker may be a promising candidate for treatments, involving lipid metabolism inhibitors, that target these cells to prevent metastasis.
Every year, 74,000 new cases of nonmelanoma skin cancer are diagnosed in Spain—a group that includes squamous cell carcinoma, the second most common cancer. The lifetime risk of battling skin cancer is between 7 percent and 11 percent and its incidence has doubled in the last 30 years.
In squamous cell carcinoma, around 4 percent of tumors metastasize and there is no tool for anticipating this. Now, however, the study led by the IMIM-Hospital del Mar provides a marker that indicates which of them are about to start migrating toward the lymph nodes to reach other organs.
The role of dyskerin
Researchers have been able to confirm the role the protein, dyskerin, plays in this process. They did so using samples from 100 primary tumors from patients with squamous cell carcinoma. In those that had metastasized, in vitro tests showed how certain noncoding RNA particles were no longer expressed and how the levels of dyskerin, which is the protein that helps to stabilize them, dropped.
In other words, these levels indicated that the tumor cells were preparing to migrate. "This is a mechanism that can explain metastasis, but not only that, it is also a marker of the moment at which the tumor cell is preparing to migrate and initiate this process," explains Dr. Inmaculada Hernández-Muñoz, PhD, the study's principal investigator.
The drop in dyskerin levels induces a metabolic change in the tumor cells, and they shift from consuming glucose to feeding on LDL molecules. This allows them to survive the migration to the lymph nodes and, from there, to other organs where they proliferate. The change is temporary and they recover their original characteristics when they have completed the process. The researchers were able to prove this using lipid metabolism markers in the analyzed samples. This marker was, indeed, present in patients prognosed with terminal-stage skin cancer.
LDL levels and risk of metastasis
In view of this fact, Hernández-Muñoz says that the study "provides a good model for understanding how tumor cells spread in the early stages of the tumor.” In fact, "it paves the way for studying whether people with higher levels of LDL cholesterol are also at greater risk of metastasis.”
The work also showed how treating the affected cells with statins—drugs used to combat high levels of LDL cholesterol—allowed the lipid metabolism to be reversed and prevented the onset of metastasis. At the same time, the researchers demonstrated that this mechanism of change in cell metabolism also occurs in other tumor types.
The study was funded by the Health Financing Fund of the Carlos III Health Institute (ISCIII) and involved the Applied Metabolomics Research Group from the IMIM-Hospital del Mar and the Proteomics Unit of the Barcelona Centre for Genomic Regulation (CRG).
- This press release was supported by the Center for Genomic Regulation