Cancerous neural invasion (CNI) is a well-known route of cancer spread in head and neck cancer. Patients with CNI suffer from severe morbidity due to neuropathic pain and most succumb to cancer within months. The exact mechanism that drives cancer cells to disseminate along nerves remained to be defined. The overall objective of our research was to identify candidate proteins and host cells that contribute to CNI. L1 cell adhesion molecule (L1cam) is a 200kDa transmembrane glycoprotein of the immunoglobulin superfamily. In many human cancers, L1cam is constitutively over-expressed, and its expression is generally associated with poor prognosis and metastases formation. Immunohistochemical analysis of the neural niche in human cancer specimens showed overexpression of L1cam in both cancer cells and Schwann cells. To address the role of L1cam in vitro, we used the Dorsal Root Ganglia. Treatment of Cancer Cells with Anti L1cam mAb resulted in a significant reduction in CNI of cancer cells. Next, we used Schwann cells conditioned media (SCCM) to study the role of soluble Schwann cells derived L1cam. Immunopercipitation of L1cam in SCCM resulted in a significant reduction in L1cam concentration and led to reduced cancer cell migration, invasion, and motility. To study the role of SCCM as a chemo attractant to cancer cells we utilized a modified in-vitro nerve invasion assay that consists of 3 layers Fibroblasts-ECM-Schwann. In this model blocking the activity of L1cam in Schwann cells inhibited the cancer cells invasion through these layers. Finally, in-vivo studies in transgenic mice treated with L1cam mAb triweekly, showed a significant reduction in CNI in the tumors compared to the control group. Taken together, our results identify a paracrine interaction between Schwann cells in the neural niche and the cancer cells promotes perineural invasion via L1cam secretion.
Citation Format: Shorook Na’ara, Ziv Gil, Moran Amit. Paracrine interactions between Schwann cells and cancer cells promotes perineural invasion via L1cam secretion. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5072.