Serum levels of cytoplasmic melanoma-associated antigen at diagnosis may predict clinical relapse in neuroblastoma patients

Abstract

The high molecular weight melanoma-associated antigen (HMW-MAA) and the cytoplasmic melanoma-associated antigen (cyt-MAA/LGALS3BP) are expressed in melanoma. Their serum levels are increased in melanoma patients and correlate with clinical outcome. We investigated whether these molecules can serve as prognostic markers for neuroblastoma (NB) patients. Expression of cyt-MAA and HMW-MAA was evaluated by flow cytometry in NB cell lines, patients’ neuroblasts (FI-NB), and short-term cultures of these latter cells (cNB). LGALS3BP gene expression was evaluated by RT–qPCR on FI-NB, cNB, and primary tumor specimens. Soluble HMW-MAA and cyt-MAA were tested by ELISA. Cyt-MAA and HMW-MAA were expressed in NB cell lines, cNB, and FI-NB samples. LGALS3BP gene expression was higher in primary tumors and cNB than in FI-NB samples. Soluble cyt-MAA, but not HMW-MAA, was detected in NB cell lines and cNBs supernatants. NB patients’ serum levels of both antigens were higher than those of the healthy children. High cyt-MAA serum levels at diagnosis associated with higher incidence of relapse, independently from other known risk factors. In conclusion, both HMW-MAA and cyt-MAA antigens, and LGALS3BP gene, were expressed by NB cell lines and patients’ neuroblasts, and both antigens’ serum levels were increased in NB patients. Elevated serum levels of cyt-MAA at diagnosis correlated with relapse, supporting that cyt-MAA may serve as early serological biomarker to individuate patients at higher risk of relapse that may require a more careful follow-up, after being validated in a larger cohort of patients at different time-points during follow-up. Given its immunogenicity, cyt-MAA may also be a potential target for NB immunotherapy.

Galectin-3 Binding Protein Secreted by Breast Cancer Cells Inhibits Monocyte-Derived Fibrocyte Differentiation

“…MDA-MB 435 accumulates high concentrations of extracellular LGALS3BP compared to other cancer cell lines (110), and patients with metastatic melanoma have higher serum LGALS3BP than patients with benign skin cancer (111). In patients with breast cancer (112, 113), ovarian cancer (114–117), or melanoma (118–120), serum LGALS3BP concentrations increase during the progression to metastasis (49, 121). An intriguing possibility is that LGALS3BP may play a role in metastasis by inhibiting monocyte-derived fibrocyte differentiation.…”

Structural deciphering of the NG2/CSPG4 proteoglycan multifunctionality

“…If not completely destroyed in the extracellular spaces, NG2/CSPG4 fragments may eventually enter the blood stream. In fact, such fragments are frequently found in peripheral blood of cancer patients for whom they may serve as an adjunct in the prognostication of the disease (65,66).…”

Plasma Levels of Soluble HLA-E and HLA-F at Diagnosis May Predict Overall Survival of Neuroblastoma Patients

“…Moreover, high serum levels of sHLA-G and CYT-MAA at diagnosis predicted a worse event-free survival (EFS), thus suggesting a potential use of these molecules as surrogate biomarkers [4, 5]. We have also demonstrated that high levels of DKK-1 associate with poor clinical response [6] and high VMA/HVA ratio associated with a better EFS, but only in patients with localized MYCN nonamplified tumors [7].…”