IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Tyrosine Isomers Mediate the Classical Phenomenon of Concomitant Tumor Resistance
Autor/es:
RAÚL A. RUGGIERO; JUAN BRUZZO; PAULA CHIARELLA; PEDRO DI GIANNI; MARTÍN A. ISTURIZ; SUSANA LINSKENS; NORMA SPEZIALE; ROBERTO P. MEISS; OSCAR D. BUSTUOABAD; CHRISTIANE D. PASQUALINI
Revista:
CANCER RESEARCH
Editorial:
AMER ASSOC CANCER RESEARCH
Referencias:
Lugar: Philadelphia; Año: 2011 vol. 71 p. 7113 - 7124
ISSN:
0008-5472
Resumen:
Abstract  Concomitant tumor resistance (CR) is a phenomenon originally described in 1906 in which a tumor-bearing 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 havehost 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, manifesta-indicated that T cell?dependent processes mediate CR in hosts bearing immunogenic small tumors, manifesta-  tions of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusivetions 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 threeserum 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 notdifferent 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 effectsgenerate 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/extracellularof 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 ofsignal-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 newdormancy. 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, angeneralized approaches to limit the development of metastases that arise after resection of primary tumors, an  issue of pivotal importance to oncologists and their patients. issue of pivotal importance to oncologists and their patients.