Detecting Protein Pathways Affecting Nerve Damage in Rat Spinal Cords with Breast Cancer and Paclitaxel Treatment via RPPA

Abstract

Paclitaxel (PAC) is a common first-line chemotherapy drug used for breast cancer treatment.  However, when treated, severe side effects of chronic pain in the nerves outside the brain and spinal cord, or neuropathic pain, occur. Although many studies explore neuropathic pain and nerve damage caused by paclitaxel treatment, they typically focus on nerve cells and pain relief methods. We examined proteins that may contribute to nerve damage in mouse spinal cords under different conditions of breast cancer and paclitaxel treatment.  To identify the different protein pathways present in PAC-treated cancer vs. untreated cancer, vehicle control with cancer vs. control without cancer, and spinal cord with both or neither conditions, we used mass spectrometry and created volcano plots. Using Reverse Phase Protein Array (RPPA), we quantified the number of specific proteins present and identified antibodies for further study. Using immunohistochemistry, we used antibody H2AX to locate this protein in neuroma tissue as a surrogate nerve tissue. RPPA results showed that breast cancer increased histone 4 and IRS-1 Ser612 compared to no cancer. Paclitaxel treatment with cancer increased H2AX and decreased autophagy-related proteins compared to untreated cancer. Currently, we are investigating specific pathways that are altered by the presence of breast cancer and the effects of paclitaxel. We found breast cancer cells can alter spinal cord proteins, which are essential for normal nerve signaling. Additionally, paclitaxel disrupts protein signaling pathways involved in nerve functions, leading to inflammation and neuropathic pain.