Molecular characteristics of cerebrospinal fluid from LMM patients


PATIENTS with advanced mela
noma who develop metastases in
the leptomeninges, the fluid filled membranes surrounding the brain and spinal cord, have an extremely dismal prognosis. Most patients only survive for 8 to 10 weeks after diagnosis. One reason for this poor prognosis is that very little information is known about the molecular development of leptomeningeal melanoma metastases (LMM), making it difficult to develop effective therapies. Researchers in Moffitt Cancer Center’s Donald A. Adam Melanoma and Skin Cancer Center of Excellence and the Department of Neuro-Oncology sought to change this by performing an extensive analysis of the molecular characteristics of the cerebrospinal fluid of patients with LMM. Their findings were published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Cancer development and progression are highly regulated by intricate interactions between cancer cells and the surrounding environment.
Melanoma cells that invade and metastasize into the leptomeninges interact with the surrounding cerebrospinal fluid. Moffitt researchers wanted to improve their understanding of the development of LMM by analyzing the protein and RNA composition of cerebrospinal fluid from patients with LMM. They compared the molecular profiles of 8 control patients without LMM to 8 patients with LMM, including one LMM patient who had an extraordinary response to treatment and was still alive more than 35 months after diagnosis.
They discovered that the cerebrospinal fluid from LMM patients was enriched for proteins involved in innate immunity, proteases and the IGF-signaling pathway. The most commonly altered protein was TGF-â1. Interestingly, the one patient who had an extraordinary response to treatment displayed high levels of these proteins at baseline, but expression levels decreased as the patient responded to treatment. However, the protein expression patterns in the remaining LMM patients who had poor responses to treatment were high at baseline and remained high throughout treatment and disease progression.
Melanoma rates decline sharply among adolescents and young adults, shows research. The researcher team, led by Keiran Smalley, Ph.D., director of the Donald A. Adam Melanoma and Skin Cancer Center of Excellence and Peter Forsyth, M.D., Chair of the Department of Neuro-Oncology, hypothesized that the cerebrospinal fluid of LMM patients could impact melanoma cells by modulating their molecular profile.