Abstract：
Cancer is a global public health issue. Neuroblastoma (NB) originates from any tissue of the sympathetic nervous system, and the most affected site is the abdomen. The adrenal gland is the primary site in 38% of cases. Approximately 50% of patients have metastatic disease at diagnosis, and bone marrow is often affected. Metastatic disease is characterized by the spreading of cancer cells that are frequently resistant to chemotherapy and radiotherapy from the primary tumor to other specific parts of the body and is responsible for 90% of cancer-related deaths. Increasing evidence has indicated that nitric oxide (NO) signaling is implicated in the pathophysiology of many types of cancer, particularly in tumorigenesis and cancer progression. However, the effect of NO on metastasis cannot be easily classified as prometastatic or antimetastatic. An understanding at the molecular level of the role of NO in cancer will have profound therapeutic implications for the diagnosis and treatment of disease. Here, the proline-rich decapeptide isolated from Bothrops jararaca venom (Bj-PRO-10c) that enhances and sustains the generation of NO was used to unravel the role of metabolic NO in steps of metastasis. Bj-PRO-10c showed an antimetastatic effect, mainly by interfering with actin cytoskeleton rearrangement, controlling cell proliferation, and decreasing the seeding efficiency of NB in metastatic niches. Therefore, we proposed that an approach for controlled NO induction with the right molecular strategies can hopefully inhibit metastasis and increase the lifespan of NB patients.
摘要：
癌症是一个全球性的公共卫生问题。神经母细胞瘤（NB）起源于交感神经系统的任何组织，受影响最大的部位是腹部。肾上腺是38％病例的主要部位。大约50%的患者在诊断时患有转移性疾病，骨髓经常受到影响。转移性疾病的特征是经常对化学疗法和放射疗法具有抗性的癌细胞从原发性肿瘤扩散到身体的其他特定部位，并导致90％的癌症相关死亡。越来越多的证据表明，一氧化氮（NO）信号与许多类型的癌症的病理生理学有关。特别是在肿瘤发生和癌症进展中。然而,NO对转移的影响不能轻易分类为前转移或抗转移。在分子水平上了解NO在癌症中的作用将对疾病的诊断和治疗具有深远的治疗意义。这里,从Bothropsjararaca毒液（Bj-PRO-10c）中分离出的富含脯氨酸的十肽可增强和维持NO的产生，用于阐明代谢NO在转移步骤中的作用。Bj-PRO-10c显示出抗转移作用，主要通过干扰肌动蛋白细胞骨架重排，控制细胞增殖，并降低NB在转移生态位中的播种效率。因此,我们提出用正确的分子策略控制NO诱导的方法有望抑制NB患者的转移并延长其寿命.
