Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/104862 https://doi.org/10.1186/s13046-021-01993-9 |
Resumo: | 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: 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 antitumor potential. 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: Our findings demonstrate that NCL could represent an innovative therapeutic cellular target for NB. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapyNeuroblastomaCell surface proteinNucleolinTargeted therapyNanotechnologyAnimalsAntineoplastic AgentsBone Marrow CellsCell Line, TumorCell MembraneCell ProliferationCell SurvivalDoxorubicinHeterograftsHumansLiposomesMiceNanoparticlesNeuroblastomaPeptidesPhosphoproteinsRNA-Binding ProteinsNeuroblastoma (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: 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 antitumor potential. 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: Our findings demonstrate that NCL could represent an innovative therapeutic cellular target for NB.Springer Nature2021-06-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/104862http://hdl.handle.net/10316/104862https://doi.org/10.1186/s13046-021-01993-9eng1756-9966Brignole, ChiaraBensa, VeronicaFonseca, Nuno A.Del Zotto, GennyBruno, SilviaCruz, Ana F.Malaguti, FabianaCarlini, BarbaraMorandi, FabioCalarco, EnzoPerri, PatriziaMoura, VeraEmionite, LauraCilli, MicheleDe Leonardis, FrancescoTondo, AnnalisaAmoroso, LoredanaConte, MassimoGaraventa, AlbertoSementa, Angela R.Corrias, Maria V.Ponzoni, MircoMoreira, João N.Pastorino, Fabioinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-01-26T21:55:23Zoai:estudogeral.uc.pt:10316/104862Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:21:29.948042Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy |
title |
Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy |
spellingShingle |
Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy Brignole, Chiara Neuroblastoma Cell surface protein Nucleolin Targeted therapy Nanotechnology Animals Antineoplastic Agents Bone Marrow Cells Cell Line, Tumor Cell Membrane Cell Proliferation Cell Survival Doxorubicin Heterografts Humans Liposomes Mice Nanoparticles Neuroblastoma Peptides Phosphoproteins RNA-Binding Proteins |
title_short |
Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy |
title_full |
Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy |
title_fullStr |
Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy |
title_full_unstemmed |
Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy |
title_sort |
Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy |
author |
Brignole, Chiara |
author_facet |
Brignole, Chiara Bensa, Veronica Fonseca, Nuno A. Del Zotto, Genny Bruno, Silvia Cruz, Ana F. Malaguti, Fabiana Carlini, Barbara Morandi, Fabio Calarco, Enzo Perri, Patrizia Moura, Vera Emionite, Laura Cilli, Michele De Leonardis, Francesco Tondo, Annalisa Amoroso, Loredana Conte, Massimo Garaventa, Alberto Sementa, Angela R. Corrias, Maria V. Ponzoni, Mirco Moreira, João N. Pastorino, Fabio |
author_role |
author |
author2 |
Bensa, Veronica Fonseca, Nuno A. Del Zotto, Genny Bruno, Silvia Cruz, Ana F. Malaguti, Fabiana Carlini, Barbara Morandi, Fabio Calarco, Enzo Perri, Patrizia Moura, Vera Emionite, Laura Cilli, Michele De Leonardis, Francesco Tondo, Annalisa Amoroso, Loredana Conte, Massimo Garaventa, Alberto Sementa, Angela R. Corrias, Maria V. Ponzoni, Mirco Moreira, João N. Pastorino, Fabio |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Brignole, Chiara Bensa, Veronica Fonseca, Nuno A. Del Zotto, Genny Bruno, Silvia Cruz, Ana F. Malaguti, Fabiana Carlini, Barbara Morandi, Fabio Calarco, Enzo Perri, Patrizia Moura, Vera Emionite, Laura Cilli, Michele De Leonardis, Francesco Tondo, Annalisa Amoroso, Loredana Conte, Massimo Garaventa, Alberto Sementa, Angela R. Corrias, Maria V. Ponzoni, Mirco Moreira, João N. Pastorino, Fabio |
dc.subject.por.fl_str_mv |
Neuroblastoma Cell surface protein Nucleolin Targeted therapy Nanotechnology Animals Antineoplastic Agents Bone Marrow Cells Cell Line, Tumor Cell Membrane Cell Proliferation Cell Survival Doxorubicin Heterografts Humans Liposomes Mice Nanoparticles Neuroblastoma Peptides Phosphoproteins RNA-Binding Proteins |
topic |
Neuroblastoma Cell surface protein Nucleolin Targeted therapy Nanotechnology Animals Antineoplastic Agents Bone Marrow Cells Cell Line, Tumor Cell Membrane Cell Proliferation Cell Survival Doxorubicin Heterografts Humans Liposomes Mice Nanoparticles Neuroblastoma Peptides Phosphoproteins RNA-Binding Proteins |
description |
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: 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 antitumor potential. 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: Our findings demonstrate that NCL could represent an innovative therapeutic cellular target for NB. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-02 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/104862 http://hdl.handle.net/10316/104862 https://doi.org/10.1186/s13046-021-01993-9 |
url |
http://hdl.handle.net/10316/104862 https://doi.org/10.1186/s13046-021-01993-9 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1756-9966 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134105644826624 |