Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and Invasion

Neuroblastoma, the most common pediatric extracranial solid tumor, arises from the malignant transformation of neural crest progenitors in the peripheral nervous system. Its clinical and genetic heterogeneity poses significant challenges, especially in high-risk patients with metastatic disease. Two...

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Main Authors: Diana Corallo, Cristina Nardelli, Marcella Pantile, Sara Menegazzo, Alessandra Biffi, Sanja Aveic
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Journal of Nanotheranostics
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Online Access:https://www.mdpi.com/2624-845X/5/4/13
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author Diana Corallo
Cristina Nardelli
Marcella Pantile
Sara Menegazzo
Alessandra Biffi
Sanja Aveic
author_facet Diana Corallo
Cristina Nardelli
Marcella Pantile
Sara Menegazzo
Alessandra Biffi
Sanja Aveic
author_sort Diana Corallo
collection DOAJ
description Neuroblastoma, the most common pediatric extracranial solid tumor, arises from the malignant transformation of neural crest progenitors in the peripheral nervous system. Its clinical and genetic heterogeneity poses significant challenges, especially in high-risk patients with metastatic disease. Two plastic neuroblastoma cell phenotypes, adrenergic (ADR) and mesenchymal (MES), have been identified. Notably, MES neuroblastoma cells exhibit increased migration and chemoresistance. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment further promote tumor aggressiveness by enhancing cancer cell proliferation, extracellular matrix remodeling, angiogenesis and metastasis. This study explored the role of non-activated fibroblasts in ADR and MES neuroblastoma cell proliferation, migration and invasion in vitro and in vivo. Results showed that MES and ADR neuroblastoma cells influenced fibroblast activation into CAFs differently, with MES cells promoting a more invasive environment leading to tumor spread. These findings enhance our understanding of how ADR and MES phenotypes contribute to the formation of a pro-metastatic niche by activating fibroblasts in CAFs. This insight could inform new therapeutic strategies targeting the tumor microenvironment to prevent neuroblastoma metastasis.
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spelling doaj-art-e31e561452f3419e948d07db4a9c02162024-12-27T14:33:47ZengMDPI AGJournal of Nanotheranostics2624-845X2024-12-015421222710.3390/jnt5040013Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and InvasionDiana Corallo0Cristina Nardelli1Marcella Pantile2Sara Menegazzo3Alessandra Biffi4Sanja Aveic5Laboratory of Target Discovery and Biology of Neuroblastoma, Istituto di Ricerca Pediatrica Fondazione Città della Speranza, 35127 Padova, ItalyLaboratory of Target Discovery and Biology of Neuroblastoma, Istituto di Ricerca Pediatrica Fondazione Città della Speranza, 35127 Padova, ItalyLaboratory of Target Discovery and Biology of Neuroblastoma, Istituto di Ricerca Pediatrica Fondazione Città della Speranza, 35127 Padova, ItalyLaboratory of Target Discovery and Biology of Neuroblastoma, Istituto di Ricerca Pediatrica Fondazione Città della Speranza, 35127 Padova, ItalyDivision of Pediatric Hematology, Oncology, and Stem Cell Transplant, Department of Woman’s and Child’s Health, Padua University Hospital, 35128 Padua, ItalyLaboratory of Target Discovery and Biology of Neuroblastoma, Istituto di Ricerca Pediatrica Fondazione Città della Speranza, 35127 Padova, ItalyNeuroblastoma, the most common pediatric extracranial solid tumor, arises from the malignant transformation of neural crest progenitors in the peripheral nervous system. Its clinical and genetic heterogeneity poses significant challenges, especially in high-risk patients with metastatic disease. Two plastic neuroblastoma cell phenotypes, adrenergic (ADR) and mesenchymal (MES), have been identified. Notably, MES neuroblastoma cells exhibit increased migration and chemoresistance. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment further promote tumor aggressiveness by enhancing cancer cell proliferation, extracellular matrix remodeling, angiogenesis and metastasis. This study explored the role of non-activated fibroblasts in ADR and MES neuroblastoma cell proliferation, migration and invasion in vitro and in vivo. Results showed that MES and ADR neuroblastoma cells influenced fibroblast activation into CAFs differently, with MES cells promoting a more invasive environment leading to tumor spread. These findings enhance our understanding of how ADR and MES phenotypes contribute to the formation of a pro-metastatic niche by activating fibroblasts in CAFs. This insight could inform new therapeutic strategies targeting the tumor microenvironment to prevent neuroblastoma metastasis.https://www.mdpi.com/2624-845X/5/4/13cancer-associated fibroblast (CAF)neuroblastomametastasiscell migrationtumor microenvironmentcancer dissemination
spellingShingle Diana Corallo
Cristina Nardelli
Marcella Pantile
Sara Menegazzo
Alessandra Biffi
Sanja Aveic
Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and Invasion
Journal of Nanotheranostics
cancer-associated fibroblast (CAF)
neuroblastoma
metastasis
cell migration
tumor microenvironment
cancer dissemination
title Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and Invasion
title_full Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and Invasion
title_fullStr Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and Invasion
title_full_unstemmed Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and Invasion
title_short Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and Invasion
title_sort exploring the role of fibroblasts in promoting neuroblastoma cell migration and invasion
topic cancer-associated fibroblast (CAF)
neuroblastoma
metastasis
cell migration
tumor microenvironment
cancer dissemination
url https://www.mdpi.com/2624-845X/5/4/13
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