Laboratory of Oncology, G. Gaslini Children's Hospital, Largo G. Gaslini 5, 16148 Genoa, Italy.
Cancer Immunol Immunother. 2011 Oct;60(10):1485-95. doi: 10.1007/s00262-011-1052-0. Epub 2011 Jun 10.
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.
高分子量黑色素瘤相关抗原（HMW-MAA）和细胞质黑色素瘤相关抗原（cyt-MAA/LGALS3BP）在黑色素瘤中表达。它们在黑色素瘤患者中的血清水平升高，并与临床结果相关。我们研究了这些分子是否可以作为神经母细胞瘤（NB）患者的预后标志物。通过流式细胞术在 NB 细胞系、患者的神经母细胞（(FI)-NB）和这些细胞的短期培养物（cNB）中评估 cyt-MAA 和 HMW-MAA 的表达。通过 RT-qPCR 在 (FI)-NB、cNB 和原发性肿瘤标本上评估 LGALS3BP 基因表达。通过 ELISA 测试可溶性 HMW-MAA 和 cyt-MAA。在 NB 细胞系、cNB 和 (FI)-NB 样本中均表达 cyt-MAA 和 HMW-MAA。LGALS3BP 基因表达在原发性肿瘤和 cNB 中高于 (FI)-NB 样本。在 NB 细胞系和 cNBs 上清液中检测到可溶性 cyt-MAA，但未检测到 HMW-MAA。NB 患者的两种抗原血清水平均高于健康儿童。在诊断时高 cyt-MAA 血清水平与较高的复发率相关，与其他已知危险因素无关。总之，HMW-MAA 和 cyt-MAA 抗原以及 LGALS3BP 基因均由 NB 细胞系和患者的神经母细胞表达，NB 患者的两种抗原血清水平均升高。在诊断时 cyt-MAA 血清水平升高与复发相关，支持 cyt-MAA 可作为早期血清生物标志物，以鉴定复发风险较高的患者，在更大的患者队列中在随访的不同时间点进一步验证后，这些患者可能需要更仔细的随访。鉴于其免疫原性，cyt-MAA 也可能是 NB 免疫治疗的潜在靶点。
