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Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis

BACKGROUND: Insulin-like Growth Factor Receptor-1 (IGF1R) system sustains the genesis of rhabdomyosarcoma through IGF2 autocrine overexpression. While several IGF1R-targeted strategies have been investigated to interphere with rhabdomyosarcoma growth, no attempt to neutralize IGF2 has been reported....

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Autores principales: De Giovanni, Carla, Nanni, Patrizia, Landuzzi, Lorena, Ianzano, Marianna L., Nicoletti, Giordano, Croci, Stefania, Palladini, Arianna, Lollini, Pier-Luigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367747/
https://www.ncbi.nlm.nih.gov/pubmed/30732578
http://dx.doi.org/10.1186/s12885-019-5339-4
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author De Giovanni, Carla
Nanni, Patrizia
Landuzzi, Lorena
Ianzano, Marianna L.
Nicoletti, Giordano
Croci, Stefania
Palladini, Arianna
Lollini, Pier-Luigi
author_facet De Giovanni, Carla
Nanni, Patrizia
Landuzzi, Lorena
Ianzano, Marianna L.
Nicoletti, Giordano
Croci, Stefania
Palladini, Arianna
Lollini, Pier-Luigi
author_sort De Giovanni, Carla
collection PubMed
description BACKGROUND: Insulin-like Growth Factor Receptor-1 (IGF1R) system sustains the genesis of rhabdomyosarcoma through IGF2 autocrine overexpression. While several IGF1R-targeted strategies have been investigated to interphere with rhabdomyosarcoma growth, no attempt to neutralize IGF2 has been reported. We therefore studied the possibility to hamper rhabdomyosarcoma growth with passive and active immune approaches targeting IGF2. METHODS: A murine model developing IGF2-overexpressing pelvic rhabdomyosarcoma, along with IGF2-independent salivary carcinoma, was used to investigate the efficacy and specificity of passive anti-IGFs antibody treatment. Active vaccinations with electroporated DNA plasmids encoding murine or human IGF2 were performed to elicit autochthonous anti-IGF2 antibodies. Vaccinated mice received the intravenous injection of rhabdomyosarcoma cells to study the effects of anti-IGF2 antibodies against developing metastases. RESULTS: Passive administration of antibodies neutralizing IGFs delayed the onset of IGF2-overexpressing rhabdomyosarcoma but not of IGF2-independent salivary carcinoma. A DNA vaccine against murine IGF2 did not elicit antibodies, even when combined with Treg-depletion, while a DNA vaccine encoding the human IGF2 gene elicited antibodies crossreacting with murine IGF2. Mice with anti-IGF2 antibodies were partially protected against the metastatic growth of IGF2-addicted rhabdomyosarcoma cells. CONCLUSIONS: Immune targeting of autocrine IGF2 inhibited rhabdomyosarcoma genesis and metastatic growth.
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spelling pubmed-63677472019-02-15 Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis De Giovanni, Carla Nanni, Patrizia Landuzzi, Lorena Ianzano, Marianna L. Nicoletti, Giordano Croci, Stefania Palladini, Arianna Lollini, Pier-Luigi BMC Cancer Research Article BACKGROUND: Insulin-like Growth Factor Receptor-1 (IGF1R) system sustains the genesis of rhabdomyosarcoma through IGF2 autocrine overexpression. While several IGF1R-targeted strategies have been investigated to interphere with rhabdomyosarcoma growth, no attempt to neutralize IGF2 has been reported. We therefore studied the possibility to hamper rhabdomyosarcoma growth with passive and active immune approaches targeting IGF2. METHODS: A murine model developing IGF2-overexpressing pelvic rhabdomyosarcoma, along with IGF2-independent salivary carcinoma, was used to investigate the efficacy and specificity of passive anti-IGFs antibody treatment. Active vaccinations with electroporated DNA plasmids encoding murine or human IGF2 were performed to elicit autochthonous anti-IGF2 antibodies. Vaccinated mice received the intravenous injection of rhabdomyosarcoma cells to study the effects of anti-IGF2 antibodies against developing metastases. RESULTS: Passive administration of antibodies neutralizing IGFs delayed the onset of IGF2-overexpressing rhabdomyosarcoma but not of IGF2-independent salivary carcinoma. A DNA vaccine against murine IGF2 did not elicit antibodies, even when combined with Treg-depletion, while a DNA vaccine encoding the human IGF2 gene elicited antibodies crossreacting with murine IGF2. Mice with anti-IGF2 antibodies were partially protected against the metastatic growth of IGF2-addicted rhabdomyosarcoma cells. CONCLUSIONS: Immune targeting of autocrine IGF2 inhibited rhabdomyosarcoma genesis and metastatic growth. BioMed Central 2019-02-07 /pmc/articles/PMC6367747/ /pubmed/30732578 http://dx.doi.org/10.1186/s12885-019-5339-4 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
De Giovanni, Carla
Nanni, Patrizia
Landuzzi, Lorena
Ianzano, Marianna L.
Nicoletti, Giordano
Croci, Stefania
Palladini, Arianna
Lollini, Pier-Luigi
Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis
title Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis
title_full Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis
title_fullStr Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis
title_full_unstemmed Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis
title_short Immune targeting of autocrine IGF2 hampers rhabdomyosarcoma growth and metastasis
title_sort immune targeting of autocrine igf2 hampers rhabdomyosarcoma growth and metastasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367747/
https://www.ncbi.nlm.nih.gov/pubmed/30732578
http://dx.doi.org/10.1186/s12885-019-5339-4
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