LIN28B Promotes Cancer Cell Dissemination and Angiogenesis.

Abstract

Neuroblastoma represents a major challenge in pediatric oncology with over 50% of cases involving metastasis. High-risk patients face an unfavorable prognosis, with survival rates below 40%. LIN28B plays a pivotal role in neuroblastoma development, being overexpressed in a subset of high-risk patients with widespread metastases. Here, the effect of induced LIN28B (iLIN28B) expression on neuroblastoma cells is investigated with a focus on key aspects of the metastatic cascade including anchorage, migration, invasion, and angiogenesis. iLIN28B cells show substrate-selective adherence, coating-dependent migration, and the context-guided ability to degrade the extracellular matrix. In response to tumor cell-derived IGF2, endothelial cells show enhanced motility and proliferation, while inhibition of IGF2 activity impairs LIN28B-induced angiogenesis in vitro and in vivo. These findings underscore the hub role of LIN28B in favoring pre-metastatic processes in neuroblastoma. The intricate interplay between LIN28B, endothelial cells, and the extracellular matrix contributes to the development of the aggressive neuroblastoma phenotypes.