TY - JOUR
T1 - Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article
AU - Gueron, Geraldine
AU - Anselmino, Nicolás
AU - Chiarella, Paula
AU - Ortiz, Emiliano G.
AU - Lage Vickers, Sofia
AU - Paez, Alejandra V.
AU - Giudice, Jimena
AU - Contin, Mario D.
AU - Leonardi, Daiana
AU - Jaworski, Felipe
AU - Manzano, Verónica
AU - Strazza, Ariel
AU - Montagna, Daniela R.
AU - Labanca, Estefania
AU - Cotignola, Javier
AU - Daccorso, Norma
AU - Woloszynska-Read, Anna
AU - Navone, Nora
AU - Meiss, Roberto P.
AU - Ruggiero, Raúl
AU - Vazquez, Elba
N1 - Funding Information:
We are grateful to the Prostate Cancer Foundation for the Young Investigator Award given to G.G. This work was supported by grants from the Prostate Cancer Foundation (Young Investigator award PCF), AGENCIA-PICT 2015-1786 (ARGENTINA), AGENCIA-PICT 2013-0996 (ARGENTINA), AGENCIA-PICT 2014-1590, UBACyT 2014-2017 no. 497, and the National Cancer Institute (Argentina).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41419-017-0147-8
DO - 10.1038/s41419-017-0147-8
M3 - Article
C2 - 29396431
AN - SCOPUS:85041617888
SN - 2041-4889
VL - 9
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 2
M1 - 140
ER -