Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance

Autores
Ruggiero, Raul Alejandro; Bruzzo Iraola, Juan; Chiarella, Paula; Di Gianni, Pedro; Isturiz, Martín Amadeo; Linskens, Susana Beatriz; Speziale, Norma; Meiss, Roberto P.; Bustuoabad, Oscar David; Pasqualini, Christiane D.
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Concomitant tumor resistance (CR) is a phenomenon originally described in 1906 in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although recent studies have indicated that T-cell-dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In this study, we identify this serum factor as tyrosine in its meta and ortho isoforms. In three different murine models of cancer that generate CR, both meta-tyrosine and ortho-tyrosine inhibited tumor growth. In addition, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isoforms were mediated, in part, by early inhibition of mitogen-activated protein/extracellular signal-regulated kinase pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors, an issue of pivotal importance to oncologists and their patients. ©2011 AACR.
Fil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Bruzzo Iraola, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Di Gianni, Pedro. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Linskens, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Speziale, Norma. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Pasqualini, Christiane D.. Academia Nacional de Medicina de Buenos Aires; Argentina
Materia
CONCOMITANT TUMOR RESISTANCE
TYROSINE ISOMERS
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:11336/52941
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/52941
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistanceRuggiero, Raul AlejandroBruzzo Iraola, JuanChiarella, PaulaDi Gianni, PedroIsturiz, Martín AmadeoLinskens, Susana BeatrizSpeziale, NormaMeiss, Roberto P.Bustuoabad, Oscar DavidPasqualini, Christiane D.CONCOMITANT TUMOR RESISTANCETYROSINE ISOMERShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Concomitant tumor resistance (CR) is a phenomenon originally described in 1906 in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although recent studies have indicated that T-cell-dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In this study, we identify this serum factor as tyrosine in its meta and ortho isoforms. In three different murine models of cancer that generate CR, both meta-tyrosine and ortho-tyrosine inhibited tumor growth. In addition, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isoforms were mediated, in part, by early inhibition of mitogen-activated protein/extracellular signal-regulated kinase pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors, an issue of pivotal importance to oncologists and their patients. ©2011 AACR.Fil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Bruzzo Iraola, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Di Gianni, Pedro. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Linskens, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Speziale, Norma. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Pasqualini, Christiane D.. Academia Nacional de Medicina de Buenos Aires; ArgentinaAmerican Association for Cancer Research2011-11info: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/11336/52941Ruggiero, Raul Alejandro; Bruzzo Iraola, Juan; Chiarella, Paula; Di Gianni, Pedro; Isturiz, Martín Amadeo; et al.; Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance; American Association for Cancer Research; Cancer Research; 71; 22; 11-2011; 7113-71240008-5472CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-11-0581info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/71/22/7113info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:08:58Zoai:ri.conicet.gov.ar:11336/52941instacron: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:34982025-09-29 10:08:58.484CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance
title Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance
spellingShingle Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance
Ruggiero, Raul Alejandro
CONCOMITANT TUMOR RESISTANCE
TYROSINE ISOMERS
title_short Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance
title_full Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance
title_fullStr Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance
title_full_unstemmed Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance
title_sort Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance
dc.creator.none.fl_str_mv Ruggiero, Raul Alejandro
Bruzzo Iraola, Juan
Chiarella, Paula
Di Gianni, Pedro
Isturiz, Martín Amadeo
Linskens, Susana Beatriz
Speziale, Norma
Meiss, Roberto P.
Bustuoabad, Oscar David
Pasqualini, Christiane D.
author Ruggiero, Raul Alejandro
author_facet Ruggiero, Raul Alejandro
Bruzzo Iraola, Juan
Chiarella, Paula
Di Gianni, Pedro
Isturiz, Martín Amadeo
Linskens, Susana Beatriz
Speziale, Norma
Meiss, Roberto P.
Bustuoabad, Oscar David
Pasqualini, Christiane D.
author_role author
author2 Bruzzo Iraola, Juan
Chiarella, Paula
Di Gianni, Pedro
Isturiz, Martín Amadeo
Linskens, Susana Beatriz
Speziale, Norma
Meiss, Roberto P.
Bustuoabad, Oscar David
Pasqualini, Christiane D.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CONCOMITANT TUMOR RESISTANCE
TYROSINE ISOMERS
topic CONCOMITANT TUMOR RESISTANCE
TYROSINE ISOMERS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Concomitant tumor resistance (CR) is a phenomenon originally described in 1906 in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although recent studies have indicated that T-cell-dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In this study, we identify this serum factor as tyrosine in its meta and ortho isoforms. In three different murine models of cancer that generate CR, both meta-tyrosine and ortho-tyrosine inhibited tumor growth. In addition, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isoforms were mediated, in part, by early inhibition of mitogen-activated protein/extracellular signal-regulated kinase pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors, an issue of pivotal importance to oncologists and their patients. ©2011 AACR.
Fil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Bruzzo Iraola, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Di Gianni, Pedro. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Linskens, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Speziale, Norma. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Pasqualini, Christiane D.. Academia Nacional de Medicina de Buenos Aires; Argentina
description Concomitant tumor resistance (CR) is a phenomenon originally described in 1906 in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although recent studies have indicated that T-cell-dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In this study, we identify this serum factor as tyrosine in its meta and ortho isoforms. In three different murine models of cancer that generate CR, both meta-tyrosine and ortho-tyrosine inhibited tumor growth. In addition, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isoforms were mediated, in part, by early inhibition of mitogen-activated protein/extracellular signal-regulated kinase pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors, an issue of pivotal importance to oncologists and their patients. ©2011 AACR.
publishDate 2011
dc.date.none.fl_str_mv 2011-11
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/11336/52941
Ruggiero, Raul Alejandro; Bruzzo Iraola, Juan; Chiarella, Paula; Di Gianni, Pedro; Isturiz, Martín Amadeo; et al.; Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance; American Association for Cancer Research; Cancer Research; 71; 22; 11-2011; 7113-7124
0008-5472
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52941
identifier_str_mv Ruggiero, Raul Alejandro; Bruzzo Iraola, Juan; Chiarella, Paula; Di Gianni, Pedro; Isturiz, Martín Amadeo; et al.; Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance; American Association for Cancer Research; Cancer Research; 71; 22; 11-2011; 7113-7124
0008-5472
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-11-0581
info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/71/22/7113
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 American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
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 13.070432

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