The Role of Post Traumatic Stress and Substance P in Melanoma Brain Metastasis

描述（由申请人提供）：黑色素瘤是美国最常见的癌症之一。虽然黑色素瘤起源于皮肤，但这种疾病的死亡是由于其快速转移的倾向，尤其是皮肤、淋巴结和大脑。在本研究中，我们将研究认知应激在黑色素瘤脑转移过程中可能发挥的作用。我们已经发现，黑色素瘤脑肿瘤与淋巴结肿瘤的不同之处在于，它们存在一种P物质的细胞表面受体，叫做NKR1。P物质是一种与疼痛、焦虑和抑郁有关的神经递质。在从大脑中分离出来的黑色素瘤细胞中，而不是从身体其他部位分离出来的黑色素瘤细胞中，P物质能够驱动向其来源迁移并促进其增殖，这表明它在脑转移中起着特定的作用。我们发现，增加小鼠焦虑的刺激也会促进脑内肿瘤的生长，而这一过程可以被NK1R拮抗剂抑制。这就提出了抑郁和焦虑等认知状态可能促进黑色素瘤脑转移和肿瘤生长的可能性。本研究试图在现有数据的支持下，进一步检验P物质与NKR1在这一过程中可能存在的关系。

DESCRIPTION (provided by applicant): Melanoma is one of the most common forms of cancer in the United States. While melanoma originates in the skin, death from this disease is due to its propensity to rapidly metastasize, with a preference to the skin, lymph nodes and brain. In this study we will study the role the cognitive stress may play during the process of melanoma brain metastasis. We have discovered that melanoma brain tumors differ from their lymph node counterparts by the presence of a cell surface receptor for substance P, called NKR1. Substance P is a neurotransmitter involved in pain, anxiety and depression. In melanoma cells isolated from the brain, but not those isolated from other sites in the body, substance P is able to drive migration towards its source and promote their proliferation, suggesting that it plays a specific role in brain metastasis. We have found that stimuli that increase anxiety in mice also promote intracerebral tumor growth and that this process can be inhibited by NK1R antagonists. This raises the possibility that cognitive states such as depression and anxiety may promote melanoma brain metastasis and tumor growth. This study seeks to further test the possible relationship between substance P and NKR1 in this process supported by our current data.