They lack the ability of the cancer cells to access different parts of the genomic toolbox. The immune cells in the CSF, by contrast, are hamstrung. The cancer cell can look through its genome - the entire set of DNA - and deploy the genes that give it a critical survival advantage. “It’s nefarious, the way the cancer cells exploit Lipocalin-2 to gain an advantage over the immune cells,” Dr. It’s like creating a stronger magnet than the immune cells to pick up more paper clips. But in the CSF, the cancer cells boost their Lipocalin-2 protein levels to outcompete the immune cells for iron in the surroundings. Immune cells use this protein too, when they are fighting bacteria. The protein made by this gene binds iron. The analysis revealed that the cancer cells increase their activity of a gene called Lipocalin-2. They collaborated with the laboratory of Dana Pe’er to conduct a test called single cell RNA sequencing of the cancer cells in the fluid. To investigate how cancer cells survive in CSF, the researchers analyzed fluid samples taken from five patients with leptomeningeal metastasis. They say the finding also points to a possible strategy for treatment. “It’s really unique biology that allows them to win the competition.” The researchers published their discovery on July 16 in Science. “It’s an elegant solution on the part of the cancer cell,” Dr. By hogging this nutrient, the cancer cells ensure they stay alive and grow while other cells - notably immune cells that have entered the same space - are left short. Now a team of Memorial Sloan Kettering researchers led by neuro-oncologist Adrienne Boire may have found the cancer cells’ secret power: They reprogram themselves to gobble up all the nearby iron. It has been a bit of a mystery how the cells survive in this barren environment - they seem to defy the odds and have no obvious weak spot to target. There is a dearth of iron in the area that cancer cells rely on to support their growth. In addition, doctors have been puzzled by how the cancer cells grow in CSF. This information describes leptomeningeal metastases and explains how they are treated. Radiation therapy is difficult to give without damaging the spinal cord or brain function. Normally this barrier protects the brain and spinal cord, but when cancer cells manage to invade the space, it’s hard for treatments like chemotherapy to penetrate. One reason is that this fluid, called cerebrospinal fluid (CSF), is largely sealed off from the rest of the body by a tight barrier. In the past 20 years, it’s become more common because people are living longer after treatment of their primary tumors.Ĭurrent treatments for leptomeningeal metastasis are chemotherapy and radiation therapy, but neither is very effective at destroying the cancer cells. The condition, called leptomeningeal metastasis, may cause pain, seizures, difficulty thinking, and a loss of muscle, bowel, and bladder control. A new discovery shows the cancer cells reprogram themselves to outcompete other cells for iron.Ĭancer that spreads to the fluid and tissues surrounding the brain and spinal cord can have devastating effects. It was not clear how the cancer cells survive in this space. Cerebrospinal fluid CSF leak.Cancer that has spread to the fluid and tissues of the brain and spinal cord, called leptomeningeal metastasis, is difficult to treat.
Cerebrospinal fluid (CSF) collection.Ĭleveland Clinic. Improving the brain delivery of chemotherapeutic drugs in childhood brain tumors. Triarico S, Maurizi P, Mastrangelo S, Attinà G, Capozza MA, Ruggiero A. Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion. Cerebrospinal Fluid (CSF) analysis and interpretation in neurocritical care for acute neurological conditions.
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