Role of CD200 in Schwann cell-breast cancer cell interaction: Changes in inflammatory mediators released from Schwann cells

Objective: Schwann cells undergo phenotypic changes when interacting with cancer cells, similar to nerve repair processes. These changes contribute to cancer invasion, migration, and progression. The immune modulator CD200's effects in cancer are bidirectional and vary depend on tumor type. CD200 ligand is expressed in Schwann cells and peripheral nerves, but its role in Schwann cells during breast cancer interactions remains unknown. This study aims to investigate how Schwann cell responses to metastatic breast cancer are altered in the absence of CD200. Methods: DNA was isolated from mouse ear tissue, and CD200 expression was assessed by PCR. Bilateral sciatic nerves from female Balb/c mice were excised to prepare primary CD200KO and wild type Schwann cell cultures. An orthotopic breast cancer model was established in mice, and primary tumors were excised and cultured. The secretomes of breast cancer cells were compared with Schwann cells. Cytokines (IL-6, TNF-α, IL-1β) and chemokines (CCL2, MIP-2, KC) known to activate Schwann cells and participate in metastasis were analyzed using ELISA. Additionally, the effects of minocycline, CD200fc, and Pegilayted liposomal doxorubicin (PLD) on Schwann cell responses were evaluated. Results: Exposure to the secretome of breast cancer cells increased IL-6, CCL2, MIP-2, and KC production in Schwann cells, with a more pronounced increase in CD200KO Schwann cells. Minocycline suppressed Schwann cell inflammatory responses, but the reduction in CD200KO cells was more limited compared to wild-type Schwann cells. PLD did not have a direct effect on Schwann cells; however, the response of Schwann cells to the secretome of breast cancer cells treated with PLD was significantly suppressed. Conclusion: This study is the first to demonstrate that CD200 may play a role in regulating Schwann cell immune responses in breast cancer interactions, potentially influencing tumor progression. Keywords: Schwann cell, CD200, breast cancer, cytokine, chemokine.