Abstract 6721: β3-adrenergic receptor correlates with tumor growth and progression in neuroblastoma

Abstract

Abstract Neuroblastoma (NB) is a heterogeneous, often aggressive, extracranial tumor and the most common malignancy to be diagnosed in the first year of life. It has been already demonstrated that the specific antagonism of the β3-adrenergic receptor (β3-AR) on NB tumor cells affects tumor growth. To confirm the results obtained with the pharmacological approach on the crucial role played by the β3-AR receptor in influencing different pro-tumoral signaling pathways, here we investigated the effect of CRISPR/Cas9-mediated knock-out of β3-AR gene (ADRB3) on human NB cell line BE(2)-C in vitro and in vivo. Inoculation of BE(2)-C β3-AR−/- cells in athymic nude mice (NU(N-Cr)-Foxn1nu) showed a strong reduction of NB tumor growth compared to wild type cells, and in some cases β3-AR knock-out tumor cells failed in producing a tumor mass. RNA Sequencing on these tumor masses showed alterations of signaling pathways related to various tumor mechanisms, such as proliferation, cell motility and cell differentiation. Furthermore, we evaluated by flow cytometry the expression of β3-AR in circulating tumor cells (CTCs) from NB patients with different degrees of disease. Following depletion with anti-CD45 magnetic beads, tumor cells were identified through the expression of specific tumor markers, CD56 and GD2. Results showed that a high expression of β3-AR correlates with poor prognosis, characterized by metastatic or recurrent tumors, compared to patients with a favorable clinical outcome that instead show a low expression of β3-AR. Overall, our results demonstrate the β3-AR involvement in supporting NB tumor growth and suggest a possible role in regulating the metastatic potential of this tumor. Citation Format: Alessia Boaretto, Gennaro Bruno, Nicoletta Nastasi, Claudio Favre, Maura Calvani. β3-adrenergic receptor correlates with tumor growth and progression in neuroblastoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6721.