Researchers at the University of Aarhus and the Aarhus University Hospital in Denmark discovered a specific protein associated with malignant melanomas that could be used as a marker for earlier diagnosis and potentially for the development of new therapeutic strategies. The study was published in the journal Pigment Cell & Melanoma Research and is entitled “Melanoma tumors frequently acquire LRP2/megalin expression, which modulates melanoma cell proliferation and survival rates.”
Melanoma is the most dangerous form of skin cancer caused by damage to skin cells (usually by ultraviolet radiation from sunshine or tanning beds), which triggers mutations that are not repaired, allowing cells to rapidly multiply and generate malignant tumors. Melanoma is curable when detected and treated early; if it goes undetected or if it recurs, the cancer can proliferate and spread (metastasize) to other parts of the body, becoming extremely difficult to treat. Only 10% of the patients with advanced melanoma and distant metastases survive. It is not possible to predict the spread of malignant melanomas.
Researchers found that a protein called megalin, which is known to mediate uptake and trafficking of nutrients and signaling molecules, can be detected in particularly aggressive malignant melanoma cells, and that its presence could be used as an indicator of cancer metastasis. Downregulation of megalin expression significantly decreased melanoma cell proliferation and survival rates, which led researchers to suggest that megalin improves cancer cells’ capacity to divide and survive.
“Our studies have shown that the protein megalin is almost always detectable in malignant melanomas, while it is rarely found in the benign counterparts. We see a clear trend that the more megalin is present, the faster the cells divide and the better they are at surviving. This therefore indicates that a high level of megalin in a malignant melanoma should be seen as a warning of particularly aggressive cancer cells with extremely good conditions for spreading,” said the study’s senior author Dr. Mette Madsen in a news release.
This is a groundbreaking discovery and the first time that megalin is associated with malignant melanomas. “It is a new and interesting marker that no-one has thought of before. The preliminary results look very promising. Even though we currently see considerable progress and success from novel treatment strategies for patients with metastatic melanoma, it remains a very serious illness when it reaches later stages with spreading. In a best case scenario, this discovery can pinpoint those patients who will experience a relapse, and identify which treatment will benefit which patients the most,” said Dr. Henrik Schmidt from Aarhus University Hospital, who is currently collaborating with Dr. Madsen in further studies focusing on megalin.
The team believes that megalin could allow an earlier identification of aggressive melanomas, ultimately leading to an improvement in treatment strategies and longer survival rates for patients with malignant melanoma.
“In general, the protein is present at the surface of cells and can absorb many things from the surroundings such as nutrients. So it is therefore well suited for targeted treatment; either medicine affecting the protein and its function thereby inhibiting the proliferation of the cancer cells and their survival, or for transporting lethal drugs into the cancer cells. Since the protein is not found in all of the cells of our body, but in a limited number of places in a healthy individual, this type of treatment can be expected to have less side-effects than the treatment regimens we can offer today,” explained Dr. Madsen.
The team’s next goal is to establish how megalin levels correlate with malignant melanoma metastases and patient survival.