The metastasis-promoting action of type plasminogen activator (tPA) has been blocked by preventing it from connecting to low-density lipoprotein receptor-related protein 1 (LRP1), proposed Heissig's research team. Melanoma skin cancer //tumors grow larger and are more likely to metastasize due to interactions between a pair of molecules, according to experiments in mice and human cells. The results may restore the potential for a type of cancer therapy previously abandoned in clinical trials. The results also implicate one molecule already connected to obesity and dementia as a potential cause of metastasis, or spread of cancer cells to other areas of the body.
‘LRP1 linked to chronic diseases including diabetes, obesity, and Alzheimer's disease.’
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Melanoma accounts for about 1 percent of skin cancers, but causes a large majority of skin cancer deaths, according to the American Cancer Society. Few treatments exist to prevent melanoma from metastasizing. A research team led by Associate Professor Beate Heissig at the University of Tokyo Institute of Medical Science has studied tissue type plasminogen activator (tPA) for over a decade. tPA is a protease, a small molecule that can cut proteins. tPA bonds to a larger protein that sits within the membrane barrier of animal cells, called low-density lipoprotein receptor-related protein 1 (LRP1).
"It's surprising that LRP1 is also regulating cancer growth and spread. It's normally a receptor for fat molecules," said Heissig.
Controlling cancer's spread
In 2016, Heissig's research group discovered that mice given extra tPA had greater numbers of a specific type of cell. This same cell type usually increases within the melanoma tumors and can enhance tumor growth. Based on that potential connection, the current project was designed to investigate what role tPA might play in skin cancer.
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Clinical researchers have attempted to prevent metastasis by stopping proteases. However, completely blocking all proteases causes unintended side effects. No protease-based cancer therapy has succeeded in clinical trials.
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Salama also suggests that tPA may be linked to cancer immunotherapy, the life-saving treatment awarded the 2018 Nobel Prize in Physiology or Medicine.
"The scientific community knows that tPA can interfere with the cell signals being studied for cancer immunotherapy. Blocking tPA could enhance the immune system's action and potentially boost the effectiveness of cancer immunotherapy treatments," said Salama.
Source-Eurekalert