Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Cell death & disease - 9(2018), 2 vom: 02. Feb., Seite 140 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gueron, Geraldine [VerfasserIn] |
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| Links: |
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| Themen: |
3-tyrosine |
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| Anmerkungen: |
Date Completed 02.08.2019 Date Revised 02.08.2019 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41419-017-0147-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM280563388 |
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| 245 | 1 | 0 | |a Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis |
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| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Anselmino, Nicolás |e verfasserin |4 aut | |
| 700 | 1 | |a Chiarella, Paula |e verfasserin |4 aut | |
| 700 | 1 | |a Ortiz, Emiliano G |e verfasserin |4 aut | |
| 700 | 1 | |a Lage Vickers, Sofia |e verfasserin |4 aut | |
| 700 | 1 | |a Paez, Alejandra V |e verfasserin |4 aut | |
| 700 | 1 | |a Giudice, Jimena |e verfasserin |4 aut | |
| 700 | 1 | |a Contin, Mario D |e verfasserin |4 aut | |
| 700 | 1 | |a Leonardi, Daiana |e verfasserin |4 aut | |
| 700 | 1 | |a Jaworski, Felipe |e verfasserin |4 aut | |
| 700 | 1 | |a Manzano, Verónica |e verfasserin |4 aut | |
| 700 | 1 | |a Strazza, Ariel |e verfasserin |4 aut | |
| 700 | 1 | |a Montagna, Daniela R |e verfasserin |4 aut | |
| 700 | 1 | |a Labanca, Estefania |e verfasserin |4 aut | |
| 700 | 1 | |a Cotignola, Javier |e verfasserin |4 aut | |
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| 700 | 1 | |a Ruggiero, Raúl |e verfasserin |4 aut | |
| 700 | 1 | |a Vazquez, Elba |e verfasserin |4 aut | |
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