# LIN28B Promotes Cancer Cell Dissemination and Angiogenesis

## TL;DR

This study shows that the LIN28B gene promotes cancer spread and blood vessel growth in neuroblastoma, a deadly childhood cancer.

## Contribution

The study reveals how LIN28B drives metastasis and angiogenesis in neuroblastoma through the IGF2-IGF1R pathway.

## Key findings

- iLIN28B cells exhibit substrate-selective adherence and migration, and can degrade the extracellular matrix.
- LIN28B-induced angiogenesis is mediated by tumor cell-derived IGF2 and inhibited by blocking IGF2 activity.
- LIN28B plays a central role in promoting aggressive neuroblastoma phenotypes through interactions with endothelial cells.

## 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.

Children diagnosed with high‐risk neuroblastoma have a 5‐year event‐free survival rate of less than 50% and poor outcomes after recurrence. Deregulation of the LIN28B oncogene can be addressed in these patients. Upregulation of LIN28B is shown to support the metastatic cascade. By regulating the IGF2‐IGF1R axis, LIN28B triggers angiogenesis and facilitates the spread of cancer cells.