INVESTIGADORES
VAZQUEZ Elba Susana
artículos
Título:
Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis
Autor/es:
GUERON, GERALDINE; ANSELMINO, NICOLÁS; CHIARELLA, PAULA; ORTIZ, EMILIANO G.; LAGE VICKERS, SOFIA; PAEZ, ALEJANDRA V.; GIUDICE, JIMENA; CONTIN, MARIO D.; LEONARDI, DAIANA; JAWORSKI, FELIPE; MANZANO, VERÓNICA; STRAZZA, ARIEL; MONTAGNA, DANIELA R.; LABANCA, ESTEFANIA; COTIGNOLA, JAVIER; D´ACCORSO, NORMA; WOLOSZYNSKA-READ, ANNA; NAVONE, NORA; MEISS, ROBERTO P.; RUGGIERO, RAÚL; VAZQUEZ, ELBA
Revista:
Cell Death & Disease
Editorial:
e-ISSN: 1350-9047 - Cell Death Disease
Referencias:
Lugar: Londres; Año: 2018 vol. 9
Resumen:
An abrupt increase in metastatic growth as a consequence of the removal of primary tumors suggests that the concomitant resistance (CR) phenomenon might occur in human cancer. CR occurs in murine tumors and ROS-damaged phenylalanine, meta-tyrosine (m-Tyr), was proposed as the serum anti-tumor factor primarily responsible for CR. Herein, we demonstrate for the first time that CR happens in different experimental human solid tumors (prostate, lung anaplastic, and nasopharyngeal carcinoma). Moreover, m-Tyr was detected in the serum of mice bearing prostate cancer (PCa) xeno grafts. Primary tumor growth was inhibited in animals injected with m-Tyr. Further, the CR phenomenon was reversed when secondary implants were injected into mice with phenylalanine (Phe), a protective amino acid highly present in primary tumors. PCa cells exposed to m-Tyr in vitro showed reduced cell viability, down regulated NFκB/STAT3/Notch axis, and induced autophagy; effects reversed by Phe. Strikingly, m-Tyr administration also impaired both, spontaneous metastasis derived from murine mammary carcinomas (4T1, C7HI, and LMM3) and PCa experimental metastases. Altogether, our findings propose m-Tyr delivery as a novel approach to boost the therapeutic efficacy of the current treatment for metastasis preventing the escape from tumor dormancy