Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control
- Autores
- Ruggiero, Raul Alejandro; Bruzzo Iraola, Juan; Chiarella, Paula; Bustuoabad, Oscar David; Meiss, Roberto P.; Pasqualini, Christiane D.
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although previous studies 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 a recently published study, we identified this factor as meta-tyrosine and ortho-tyrosine, 2 isomers of tyrosine that would not be present in normal proteins. In 3 different murine models of cancer that generate CR, both meta- and orthotyrosine inhibited tumor growth. Additionally, 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 isomers were mediated in part by early inhibition of the MAP/ERK pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy in G 0-phase. Other mechanisms, putatively involving the activation of an intra-S-phase checkpoint, would also inhibit tumor proliferation by accumulating cells in S-phase. 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 or after other stressors that may promote the escape of metastases from dormancy, an issue that is of pivotal importance to oncologists and their patients. ©2012 AACR.
Fil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bruzzo Iraola, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Pasqualini, Christiane D.. Academia Nacional de Medicina de Buenos Aires; Argentina - Materia
-
Tyrosine Isomers
Metastases Control - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/52949
Ver los metadatos del registro completo
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Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases controlRuggiero, Raul AlejandroBruzzo Iraola, JuanChiarella, PaulaBustuoabad, Oscar DavidMeiss, Roberto P.Pasqualini, Christiane D.Tyrosine IsomersMetastases Controlhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although previous studies 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 a recently published study, we identified this factor as meta-tyrosine and ortho-tyrosine, 2 isomers of tyrosine that would not be present in normal proteins. In 3 different murine models of cancer that generate CR, both meta- and orthotyrosine inhibited tumor growth. Additionally, 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 isomers were mediated in part by early inhibition of the MAP/ERK pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy in G 0-phase. Other mechanisms, putatively involving the activation of an intra-S-phase checkpoint, would also inhibit tumor proliferation by accumulating cells in S-phase. 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 or after other stressors that may promote the escape of metastases from dormancy, an issue that is of pivotal importance to oncologists and their patients. ©2012 AACR.Fil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bruzzo Iraola, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Pasqualini, Christiane D.. Academia Nacional de Medicina de Buenos Aires; ArgentinaAmerican Association for Cancer Research2012-03info: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/11336/52949Ruggiero, Raul Alejandro; Bruzzo Iraola, Juan; Chiarella, Paula; Bustuoabad, Oscar David; Meiss, Roberto P.; et al.; Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control; American Association for Cancer Research; Cancer Research; 72; 5; 3-2012; 1043-10500008-5472CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-11-2964info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/72/5/1043info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:06:32Zoai:ri.conicet.gov.ar:11336/52949instacron: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 10:06:32.405CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control |
title |
Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control |
spellingShingle |
Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control Ruggiero, Raul Alejandro Tyrosine Isomers Metastases Control |
title_short |
Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control |
title_full |
Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control |
title_fullStr |
Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control |
title_full_unstemmed |
Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control |
title_sort |
Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control |
dc.creator.none.fl_str_mv |
Ruggiero, Raul Alejandro Bruzzo Iraola, Juan Chiarella, Paula Bustuoabad, Oscar David Meiss, Roberto P. Pasqualini, Christiane D. |
author |
Ruggiero, Raul Alejandro |
author_facet |
Ruggiero, Raul Alejandro Bruzzo Iraola, Juan Chiarella, Paula Bustuoabad, Oscar David Meiss, Roberto P. Pasqualini, Christiane D. |
author_role |
author |
author2 |
Bruzzo Iraola, Juan Chiarella, Paula Bustuoabad, Oscar David Meiss, Roberto P. Pasqualini, Christiane D. |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
Tyrosine Isomers Metastases Control |
topic |
Tyrosine Isomers Metastases Control |
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 in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although previous studies 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 a recently published study, we identified this factor as meta-tyrosine and ortho-tyrosine, 2 isomers of tyrosine that would not be present in normal proteins. In 3 different murine models of cancer that generate CR, both meta- and orthotyrosine inhibited tumor growth. Additionally, 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 isomers were mediated in part by early inhibition of the MAP/ERK pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy in G 0-phase. Other mechanisms, putatively involving the activation of an intra-S-phase checkpoint, would also inhibit tumor proliferation by accumulating cells in S-phase. 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 or after other stressors that may promote the escape of metastases from dormancy, an issue that is of pivotal importance to oncologists and their patients. ©2012 AACR. Fil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Bruzzo Iraola, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Meiss, Roberto P.. 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 in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although previous studies 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 a recently published study, we identified this factor as meta-tyrosine and ortho-tyrosine, 2 isomers of tyrosine that would not be present in normal proteins. In 3 different murine models of cancer that generate CR, both meta- and orthotyrosine inhibited tumor growth. Additionally, 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 isomers were mediated in part by early inhibition of the MAP/ERK pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy in G 0-phase. Other mechanisms, putatively involving the activation of an intra-S-phase checkpoint, would also inhibit tumor proliferation by accumulating cells in S-phase. 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 or after other stressors that may promote the escape of metastases from dormancy, an issue that is of pivotal importance to oncologists and their patients. ©2012 AACR. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-03 |
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/11336/52949 Ruggiero, Raul Alejandro; Bruzzo Iraola, Juan; Chiarella, Paula; Bustuoabad, Oscar David; Meiss, Roberto P.; et al.; Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control; American Association for Cancer Research; Cancer Research; 72; 5; 3-2012; 1043-1050 0008-5472 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/52949 |
identifier_str_mv |
Ruggiero, Raul Alejandro; Bruzzo Iraola, Juan; Chiarella, Paula; Bustuoabad, Oscar David; Meiss, Roberto P.; et al.; Concomitant tumor resistance: The role of tyrosine isomers in the mechanisms of metastases control; American Association for Cancer Research; Cancer Research; 72; 5; 3-2012; 1043-1050 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-11-2964 info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/72/5/1043 |
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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1844613915650031616 |
score |
13.070432 |