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

描述(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，但死于这种疾病的原因是它容易迅速转移，偏爱皮肤、淋巴结和大脑。在这项研究中，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，黑色素瘤脑瘤与其相应的淋巴结瘤的不同之处在于细胞表面存在一种P物质受体，称为NKR1。P物质是一种神经递质，与疼痛、焦虑和抑郁有关。在从大脑分离的黑色素瘤细胞中，P物质能够推动黑色素瘤细胞向其来源迁移并促进其增殖，这表明它在脑转移中发挥着特定的作用。我们发现，增加小鼠焦虑的刺激也会促进脑内肿瘤的生长，这一过程可以被NK1R拮抗剂抑制。这增加了抑郁和焦虑等认知状态可能会促进黑色素瘤脑转移和肿瘤生长的可能性。这项研究试图进一步检验P物质和NKR1在这一过程中的可能关系，这是我们目前的数据支持的。

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.