Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article
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...
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2018
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v9_n2_p_Gueron http://hdl.handle.net/20.500.12110/paper_20414889_v9_n2_p_Gueron |
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paper:paper_20414889_v9_n2_p_Gueron2023-06-08T16:33:11Z Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis article 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). 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v9_n2_p_Gueron 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 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). |
| 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 |
| publishDate |
2018 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v9_n2_p_Gueron http://hdl.handle.net/20.500.12110/paper_20414889_v9_n2_p_Gueron |
| _version_ |
1768544887900209152 |