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spelling todo:paper_20414889_v9_n2_p_Gueron2023-10-03T16:37:57Z Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article Gueron, G. Anselmino, N. Chiarella, P. Ortiz, E.G. Lage Vickers, S. Paez, A.V. Giudice, J. Contin, M.D. Leonardi, D. Jaworski, F. Manzano, V. Strazza, A. Montagna, D.R. Labanca, E. Cotignola, J. Daccorso, N. Woloszynska-Read, A. Navone, N. Meiss, R.P. Ruggiero, R. Vazquez, E. immunoglobulin enhancer binding protein meta tyrosine Notch receptor phenylalanine STAT3 protein amino acid blood level animal cell animal experiment animal model animal tissue antiproliferative activity Article autophagy cancer growth cancer inhibition cancer resistance cell viability controlled study down regulation drug mechanism experimental metastasis human human cell in vitro study lung cancer male mouse nasopharynx carcinoma nonhuman primary tumor priority journal prostate cancer solid malignant neoplasm 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) xenografts. 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, downregulated 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. © 2018 The Author(s). JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_20414889_v9_n2_p_Gueron
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic immunoglobulin enhancer binding protein
meta tyrosine
Notch receptor
phenylalanine
STAT3 protein
amino acid blood level
animal cell
animal experiment
animal model
animal tissue
antiproliferative activity
Article
autophagy
cancer growth
cancer inhibition
cancer resistance
cell viability
controlled study
down regulation
drug mechanism
experimental metastasis
human
human cell
in vitro study
lung cancer
male
mouse
nasopharynx carcinoma
nonhuman
primary tumor
priority journal
prostate cancer
solid malignant neoplasm
spellingShingle immunoglobulin enhancer binding protein
meta tyrosine
Notch receptor
phenylalanine
STAT3 protein
amino acid blood level
animal cell
animal experiment
animal model
animal tissue
antiproliferative activity
Article
autophagy
cancer growth
cancer inhibition
cancer resistance
cell viability
controlled study
down regulation
drug mechanism
experimental metastasis
human
human cell
in vitro study
lung cancer
male
mouse
nasopharynx carcinoma
nonhuman
primary tumor
priority journal
prostate cancer
solid malignant neoplasm
Gueron, G.
Anselmino, N.
Chiarella, P.
Ortiz, E.G.
Lage Vickers, S.
Paez, A.V.
Giudice, J.
Contin, M.D.
Leonardi, D.
Jaworski, F.
Manzano, V.
Strazza, A.
Montagna, D.R.
Labanca, E.
Cotignola, J.
Daccorso, N.
Woloszynska-Read, A.
Navone, N.
Meiss, R.P.
Ruggiero, R.
Vazquez, E.
Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article
topic_facet immunoglobulin enhancer binding protein
meta tyrosine
Notch receptor
phenylalanine
STAT3 protein
amino acid blood level
animal cell
animal experiment
animal model
animal tissue
antiproliferative activity
Article
autophagy
cancer growth
cancer inhibition
cancer resistance
cell viability
controlled study
down regulation
drug mechanism
experimental metastasis
human
human cell
in vitro study
lung cancer
male
mouse
nasopharynx carcinoma
nonhuman
primary tumor
priority journal
prostate cancer
solid malignant neoplasm
description 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) xenografts. 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, downregulated 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. © 2018 The Author(s).
format JOUR
author Gueron, G.
Anselmino, N.
Chiarella, P.
Ortiz, E.G.
Lage Vickers, S.
Paez, A.V.
Giudice, J.
Contin, M.D.
Leonardi, D.
Jaworski, F.
Manzano, V.
Strazza, A.
Montagna, D.R.
Labanca, E.
Cotignola, J.
Daccorso, N.
Woloszynska-Read, A.
Navone, N.
Meiss, R.P.
Ruggiero, R.
Vazquez, E.
author_facet Gueron, G.
Anselmino, N.
Chiarella, P.
Ortiz, E.G.
Lage Vickers, S.
Paez, A.V.
Giudice, J.
Contin, M.D.
Leonardi, D.
Jaworski, F.
Manzano, V.
Strazza, A.
Montagna, D.R.
Labanca, E.
Cotignola, J.
Daccorso, N.
Woloszynska-Read, A.
Navone, N.
Meiss, R.P.
Ruggiero, R.
Vazquez, E.
author_sort Gueron, G.
title Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article
title_short Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article
title_full Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article
title_fullStr Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article
title_full_unstemmed Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article
title_sort game-changing restraint of ros-damaged phenylalanine, upon tumor metastasis article
url http://hdl.handle.net/20.500.12110/paper_20414889_v9_n2_p_Gueron
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