Uncovering the role of netrins and DCC (deleted in colorectal cancer) in pancreatic neuroendocrine neoplasms (PNEN) tumorigenesis

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Introduction: DCC functions as a tumor suppressor and is altered in various tumors, including neuroendocrine neoplasms. Netrin (NTN)-1 serves as the primary ligand for DCC. Operating as a dependence receptor, DCC induces apoptosis without NTN and promotes cell survival in its presence. In some cancers like small cell lung cancer and neuroblastoma, upregulation of NTN-3 rather than NTN-1 has been observed. However, the precise involvement of NTNs and DCC in PNEN remains unclear.

Aim(s): Our research aims to elucidate the roles of DCC and NTNs in PNEN tumorigenesis and explore their potential for targeted treatment.

Materials and methods: In vitro experiments utilized the PNEN cell line BON1. Evaluation of DCC, NTN-1, and NTN-3 expression levels was performed using QPCR, western blotting, and ELISA. Cell viability and proliferation studies were conducted after manipulating DCC expression via DCC siRNA, utilizing varied NTN-1 concentrations, and employing an NTN scavenger antibody (NP137- NETRIS Pharma). In vivo experiments entailed monitoring the growth of BON1 xenografts in nude mice treated with NP137 or PBS.

Conference:

Presenting Author: Sela Peremen L

Authors: Sela Peremen L, Telerman A, Peshes Yaloz N, Tirosh A,

Keywords: neuroendocrine, netrin, pancreatic neuroendocrine tumor, dcc,