Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)

Autores
Recouvreux, Maria Victoria; Camilletti, María Andrea; Rifkin, Daniel B.; Becu, Damasia; Diaz, Graciela Susana
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Prolactinomas are the most prevalent type of secreting pituitary tumors in humans and generally respond well to a medical therapy with dopamine agonists. However, for patients exhibiting resistance to dopaminergic drugs, alternative treatments are desired. Antiangiogenic strategies might represent a potential therapy for these tumors. Thrombospondin 1 (TSP-1) is a large multifunctional glycoprotein involved in multiple biological processes including angiogenesis, apoptosis, and activation of TGF- 1. Because tumors that overexpress TSP-1 grow more slowly, have fewer metastases, and have decreased angiogenesis, TSP-1 provides a novel target for cancer treatment. ABT-510 and ABT-898 are TSP-1 synthetic analogs that mimic its antiangiogenic action. In the present study, we explored the potential effect of ABT-510 and ABT-898 on experimental prolactinomas induced by chronic diethylstilbestrol (DES) treatment in female rats. We demonstrated that a 2-wk treatment with ABT-510 and ABT-898 counteracted the increase in pituitary size and serum prolactin levels as well as the pituitary proliferation rate induced by DES. These inhibitory effects on tumor growth could be mediated by the antiangiogenic properties of the drugs. We also demonstrated that ABT-510 and ABT-898, in addition to their described antiangiogenic effects, increased active TGF- 1 level in the tumors. We postulate that the recovery of the local cytokine activation participates in the inhibition of lactotrope function. These results place these synthetic TSP-1 analogs as potential alternative or complementary treatments in dopamine agonist-resistant prolactinomas.
Fil: Recouvreux, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Cedars Sinai Medical Center; Estados Unidos
Fil: Camilletti, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rifkin, Daniel B.. New York University Medical Center; Estados Unidos
Fil: Becu, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Diaz, Graciela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
Prolactin
Thrombospondin
Tgf Beta
Ltbp
Oligopeptides
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/8325
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/8325
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)Recouvreux, Maria VictoriaCamilletti, María AndreaRifkin, Daniel B.Becu, DamasiaDiaz, Graciela SusanaProlactinThrombospondinTgf BetaLtbpOligopeptideshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Prolactinomas are the most prevalent type of secreting pituitary tumors in humans and generally respond well to a medical therapy with dopamine agonists. However, for patients exhibiting resistance to dopaminergic drugs, alternative treatments are desired. Antiangiogenic strategies might represent a potential therapy for these tumors. Thrombospondin 1 (TSP-1) is a large multifunctional glycoprotein involved in multiple biological processes including angiogenesis, apoptosis, and activation of TGF- 1. Because tumors that overexpress TSP-1 grow more slowly, have fewer metastases, and have decreased angiogenesis, TSP-1 provides a novel target for cancer treatment. ABT-510 and ABT-898 are TSP-1 synthetic analogs that mimic its antiangiogenic action. In the present study, we explored the potential effect of ABT-510 and ABT-898 on experimental prolactinomas induced by chronic diethylstilbestrol (DES) treatment in female rats. We demonstrated that a 2-wk treatment with ABT-510 and ABT-898 counteracted the increase in pituitary size and serum prolactin levels as well as the pituitary proliferation rate induced by DES. These inhibitory effects on tumor growth could be mediated by the antiangiogenic properties of the drugs. We also demonstrated that ABT-510 and ABT-898, in addition to their described antiangiogenic effects, increased active TGF- 1 level in the tumors. We postulate that the recovery of the local cytokine activation participates in the inhibition of lactotrope function. These results place these synthetic TSP-1 analogs as potential alternative or complementary treatments in dopamine agonist-resistant prolactinomas.Fil: Recouvreux, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Cedars Sinai Medical Center; Estados UnidosFil: Camilletti, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rifkin, Daniel B.. New York University Medical Center; Estados UnidosFil: Becu, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Diaz, Graciela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaEndocrine Society2012-06-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8325Recouvreux, Maria Victoria; Camilletti, María Andrea; Rifkin, Daniel B.; Becu, Damasia; Diaz, Graciela Susana; Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1); Endocrine Society; Endocrinology; 153; 8; 14-6-2012; 3861-38710013-72271945-7170enginfo:eu-repo/semantics/altIdentifier/doi/10.1210/en.2012-1007info:eu-repo/semantics/altIdentifier/url/http://press.endocrine.org/doi/10.1210/en.2012-1007info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404347/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:20Zoai:ri.conicet.gov.ar:11336/8325instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:11:20.904CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)
title Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)
spellingShingle Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)
Recouvreux, Maria Victoria
Prolactin
Thrombospondin
Tgf Beta
Ltbp
Oligopeptides
title_short Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)
title_full Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)
title_fullStr Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)
title_full_unstemmed Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)
title_sort Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1)
dc.creator.none.fl_str_mv Recouvreux, Maria Victoria
Camilletti, María Andrea
Rifkin, Daniel B.
Becu, Damasia
Diaz, Graciela Susana
author Recouvreux, Maria Victoria
author_facet Recouvreux, Maria Victoria
Camilletti, María Andrea
Rifkin, Daniel B.
Becu, Damasia
Diaz, Graciela Susana
author_role author
author2 Camilletti, María Andrea
Rifkin, Daniel B.
Becu, Damasia
Diaz, Graciela Susana
author2_role author
author
author
author
dc.subject.none.fl_str_mv Prolactin
Thrombospondin
Tgf Beta
Ltbp
Oligopeptides
topic Prolactin
Thrombospondin
Tgf Beta
Ltbp
Oligopeptides
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Prolactinomas are the most prevalent type of secreting pituitary tumors in humans and generally respond well to a medical therapy with dopamine agonists. However, for patients exhibiting resistance to dopaminergic drugs, alternative treatments are desired. Antiangiogenic strategies might represent a potential therapy for these tumors. Thrombospondin 1 (TSP-1) is a large multifunctional glycoprotein involved in multiple biological processes including angiogenesis, apoptosis, and activation of TGF- 1. Because tumors that overexpress TSP-1 grow more slowly, have fewer metastases, and have decreased angiogenesis, TSP-1 provides a novel target for cancer treatment. ABT-510 and ABT-898 are TSP-1 synthetic analogs that mimic its antiangiogenic action. In the present study, we explored the potential effect of ABT-510 and ABT-898 on experimental prolactinomas induced by chronic diethylstilbestrol (DES) treatment in female rats. We demonstrated that a 2-wk treatment with ABT-510 and ABT-898 counteracted the increase in pituitary size and serum prolactin levels as well as the pituitary proliferation rate induced by DES. These inhibitory effects on tumor growth could be mediated by the antiangiogenic properties of the drugs. We also demonstrated that ABT-510 and ABT-898, in addition to their described antiangiogenic effects, increased active TGF- 1 level in the tumors. We postulate that the recovery of the local cytokine activation participates in the inhibition of lactotrope function. These results place these synthetic TSP-1 analogs as potential alternative or complementary treatments in dopamine agonist-resistant prolactinomas.
Fil: Recouvreux, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Cedars Sinai Medical Center; Estados Unidos
Fil: Camilletti, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rifkin, Daniel B.. New York University Medical Center; Estados Unidos
Fil: Becu, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Diaz, Graciela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description Prolactinomas are the most prevalent type of secreting pituitary tumors in humans and generally respond well to a medical therapy with dopamine agonists. However, for patients exhibiting resistance to dopaminergic drugs, alternative treatments are desired. Antiangiogenic strategies might represent a potential therapy for these tumors. Thrombospondin 1 (TSP-1) is a large multifunctional glycoprotein involved in multiple biological processes including angiogenesis, apoptosis, and activation of TGF- 1. Because tumors that overexpress TSP-1 grow more slowly, have fewer metastases, and have decreased angiogenesis, TSP-1 provides a novel target for cancer treatment. ABT-510 and ABT-898 are TSP-1 synthetic analogs that mimic its antiangiogenic action. In the present study, we explored the potential effect of ABT-510 and ABT-898 on experimental prolactinomas induced by chronic diethylstilbestrol (DES) treatment in female rats. We demonstrated that a 2-wk treatment with ABT-510 and ABT-898 counteracted the increase in pituitary size and serum prolactin levels as well as the pituitary proliferation rate induced by DES. These inhibitory effects on tumor growth could be mediated by the antiangiogenic properties of the drugs. We also demonstrated that ABT-510 and ABT-898, in addition to their described antiangiogenic effects, increased active TGF- 1 level in the tumors. We postulate that the recovery of the local cytokine activation participates in the inhibition of lactotrope function. These results place these synthetic TSP-1 analogs as potential alternative or complementary treatments in dopamine agonist-resistant prolactinomas.
publishDate 2012
dc.date.none.fl_str_mv 2012-06-14
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/8325
Recouvreux, Maria Victoria; Camilletti, María Andrea; Rifkin, Daniel B.; Becu, Damasia; Diaz, Graciela Susana; Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1); Endocrine Society; Endocrinology; 153; 8; 14-6-2012; 3861-3871
0013-7227
1945-7170
url http://hdl.handle.net/11336/8325
identifier_str_mv Recouvreux, Maria Victoria; Camilletti, María Andrea; Rifkin, Daniel B.; Becu, Damasia; Diaz, Graciela Susana; Thrombospondin-1 (TSP-1) Analogs ABT-510 and ABT- 898 Inhibit Prolactinoma Growth and Recover Active Pituitary Transforming Growth Factor-b1 (TGF-b1); Endocrine Society; Endocrinology; 153; 8; 14-6-2012; 3861-3871
0013-7227
1945-7170
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2012-1007
info:eu-repo/semantics/altIdentifier/url/http://press.endocrine.org/doi/10.1210/en.2012-1007
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404347/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Endocrine Society
publisher.none.fl_str_mv Endocrine Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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