Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy.
Animals
Antineoplastic Agents
/ chemistry
Bone Marrow Cells
/ drug effects
Cell Line, Tumor
Cell Membrane
/ genetics
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Doxorubicin
/ chemistry
Heterografts
Humans
Liposomes
/ chemistry
Mice
Nanoparticles
/ chemistry
Neuroblastoma
/ drug therapy
Peptides
/ chemistry
Phosphoproteins
/ genetics
RNA-Binding Proteins
/ genetics
Nucleolin
Cell surface protein
Nanotechnology
Neuroblastoma
Nucleolin
Targeted therapy
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
02 Jun 2021
02 Jun 2021
Historique:
received:
24
02
2021
accepted:
24
05
2021
entrez:
3
6
2021
pubmed:
4
6
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Nucleolin (NCL) is a protein overexpressed and partially localized on the cell surface of tumor cells of adult cancers. Little is known about NCL and pediatric tumors and nothing is reported about cell surface NCL and NB. NB cell lines, Schwannian stroma-poor NB tumors and bone marrow (BM)-infiltrating NB cells were evaluated for the expression of cell surface NCL by Flow Cytometry, Imaging Flow Cytometry and Immunohistochemistry analyses. The cytotoxic activity of doxorubicin (DXR)-loaded nanocarriers decorated with the NCL-recognizing F3 peptide (T-DXR) was evaluated in terms of inhibition of NB cell proliferation and induction of cell death in vitro, whereas metastatic and orthotopic animal models of NB were used to examine their in vivo anti-tumor potential. NB cell lines, NB tumor cells (including patient-derived and Patient-Derived Xenografts-PDX) and 70% of BM-infiltrating NB cells show cell surface NCL expression. NCL staining was evident on both tumor and endothelial tumor cells in NB xenografts. F3 peptide-targeted nanoparticles, co-localizing with cell surface NCL, strongly associates with NB cells showing selective tumor cell internalization. T-DXR result significantly more effective, in terms of inhibition of cell proliferation and reduction of cell viability in vitro, and in terms of delay of tumor growth in all NB animal model tested, when compared to both control mice and those treated with the untargeted formulation. Our findings demonstrate that NCL could represent an innovative therapeutic cellular target for NB.
Sections du résumé
BACKGROUND
BACKGROUND
Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Nucleolin (NCL) is a protein overexpressed and partially localized on the cell surface of tumor cells of adult cancers. Little is known about NCL and pediatric tumors and nothing is reported about cell surface NCL and NB.
METHODS
METHODS
NB cell lines, Schwannian stroma-poor NB tumors and bone marrow (BM)-infiltrating NB cells were evaluated for the expression of cell surface NCL by Flow Cytometry, Imaging Flow Cytometry and Immunohistochemistry analyses. The cytotoxic activity of doxorubicin (DXR)-loaded nanocarriers decorated with the NCL-recognizing F3 peptide (T-DXR) was evaluated in terms of inhibition of NB cell proliferation and induction of cell death in vitro, whereas metastatic and orthotopic animal models of NB were used to examine their in vivo anti-tumor potential.
RESULTS
RESULTS
NB cell lines, NB tumor cells (including patient-derived and Patient-Derived Xenografts-PDX) and 70% of BM-infiltrating NB cells show cell surface NCL expression. NCL staining was evident on both tumor and endothelial tumor cells in NB xenografts. F3 peptide-targeted nanoparticles, co-localizing with cell surface NCL, strongly associates with NB cells showing selective tumor cell internalization. T-DXR result significantly more effective, in terms of inhibition of cell proliferation and reduction of cell viability in vitro, and in terms of delay of tumor growth in all NB animal model tested, when compared to both control mice and those treated with the untargeted formulation.
CONCLUSIONS
CONCLUSIONS
Our findings demonstrate that NCL could represent an innovative therapeutic cellular target for NB.
Identifiants
pubmed: 34078433
doi: 10.1186/s13046-021-01993-9
pii: 10.1186/s13046-021-01993-9
pmc: PMC8170797
doi:
Substances chimiques
Antineoplastic Agents
0
Liposomes
0
Peptides
0
Phosphoproteins
0
RNA-Binding Proteins
0
Doxorubicin
80168379AG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
180Subventions
Organisme : Ministero della Salute
ID : ER-2015-2360441-Eranet
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG18474
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG24397
Organisme : European Regional Development Fund
ID : ODD4PEGASEMP
Organisme : Fundação para a Ciência e a Tecnologia
ID : ENMed/0005/2015
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