2. Academic Validation
  3. LIN28B Promotes Cancer Cell Dissemination and Angiogenesis

LIN28B Promotes Cancer Cell Dissemination and Angiogenesis

  • Adv Biol (Weinh). 2025 Jul 18:e00730. doi: 10.1002/adbi.202400730.
Diana Corallo 1,  Sara Menegazzo 1 2,  Marcella Pantile 1,  Silvia Bresolin 3,  Carlo Zanon 3,  Alessandro Davini 1,  Massimiliano Mazzone 4,  Alessandra Biffi 2 5,  Sanja Aveic 1 6
Affiliations

Affiliations

  • 1 Laboratory of Target Discovery and Biology of Neuroblastoma, Pediatric Hematology, Oncology and Hematopoietic Cell&Gene Therapy Research Area, Institute of Pediatric Research, Fondazione Città della Speranza, Padua, 35127, Italy.
  • 2 Division of Pediatric Hematology, Oncology, and Stem Cell Transplant, Department of Woman's and Child's Health, University of Padua, Padua, 35128, Italy.
  • 3 Institute of Pediatric Research, Fondazione Città della Speranza, Padua, 35127, Italy.
  • 4 Laboratory of Tumor Inflammation and Angiogenesis, VIB KU Leuven Center for Cancer Biology, Leuven, 3000, Belgium.
  • 5 Pediatric Hematology, Oncology and Hematopoietic Cell&Gene Therapy Research Area, Institute of Pediatric Research, Fondazione Città della Speranza, Padua, 35127, Italy.
  • 6 Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, 52074, Aachen, Germany.
PMID: 40679030 DOI: 10.1002/adbi.202400730
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.

Keywords

LIN28B; angiogenesis; migration; neuroblastoma; pre‐metastatic niche.

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