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.
Mental stress has been shown to be associated with increased intracerebral substance P levels and a worse prognosis for melanoma patients. As substance P promotes tumor cell proliferation and migration and melanoma cells express its cognate receptor NK1R, we hypothesize that mental stress can negatively impact the survival of melanoma patients.