Cargando…

Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells

Background: Dietary tyrosine regulating melanoma progression has been well-recognized. However, whether tyrosine-based melanin anabolism contributes to pulmonary and cerebral organotropic colonization of melanoma remains elusive. Furthermore, approaches based on targeting tyrosinase activity to inhi...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Xuefeng, Chen, Yu, Lan, Bin, Wang, Yu, Lin, Wansong, Jiang, Xu, Ye, Jiayin, Shang, Bingxue, Feng, Chao, Liu, Jun, Zhai, Jingjie, Xu, Muhan, Li, Qing, Lin, Liangyu, Hu, Mingyuan, Zheng, Fanjun, Chen, Ling, Shao, Changshun, Wang, Ying, Shi, Yufang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899568/
https://www.ncbi.nlm.nih.gov/pubmed/35265199
http://dx.doi.org/10.7150/thno.69198
_version_ 1784663944582922240
author Wang, Xuefeng
Chen, Yu
Lan, Bin
Wang, Yu
Lin, Wansong
Jiang, Xu
Ye, Jiayin
Shang, Bingxue
Feng, Chao
Liu, Jun
Zhai, Jingjie
Xu, Muhan
Li, Qing
Lin, Liangyu
Hu, Mingyuan
Zheng, Fanjun
Chen, Ling
Shao, Changshun
Wang, Ying
Shi, Yufang
author_facet Wang, Xuefeng
Chen, Yu
Lan, Bin
Wang, Yu
Lin, Wansong
Jiang, Xu
Ye, Jiayin
Shang, Bingxue
Feng, Chao
Liu, Jun
Zhai, Jingjie
Xu, Muhan
Li, Qing
Lin, Liangyu
Hu, Mingyuan
Zheng, Fanjun
Chen, Ling
Shao, Changshun
Wang, Ying
Shi, Yufang
author_sort Wang, Xuefeng
collection PubMed
description Background: Dietary tyrosine regulating melanoma progression has been well-recognized. However, whether tyrosine-based melanin anabolism contributes to pulmonary and cerebral organotropic colonization of melanoma remains elusive. Furthermore, approaches based on targeting tyrosinase activity to inhibiting multi-organ metastasis of melanoma cells need to be designed and validated. Methods: Patients derived melanoma cells and mouse B16 melanoma cells with different pigmentation were employed in this investigation. Tyrosine content dynamics in tumors and multiple organs during the melanoma progression was monitored, and tyrosine-based melanin synthesis of melanoma cells derived from multi-organ was determined. Additionally, we also adopted RNA-seq, flow cytometry, real-time PCR and composite metastasis mouse model to analyze organotropic colonization and to validate designed therapeutic strategies. Results: B16 melanoma cells with high activity of tyrosinase and sensitivity of tyrosine utilization for melanin synthesis (Tyr-H cells) easily colonized in the lung, while B16 melanoma cells lacking above characteristics (Tyr-L cells) exhibited potent proliferation in the brain. Mechanistically, Tyr-H cells recruited and trained neutrophils and macrophages to establish pulmonary metastatic niche dependent on highly secreted CXCL1 and CXCL2 and an excessive melanosome accumulation-induced cell death. Tyr-L cells enhanced PD-L1 expression in tumor-infiltrated macrophages when they are progressing in the brain. Accordingly, intervention of tyrosinase activity (2-Ethoxybenzamide or hydroquinone) in combination with inhibitors of phagocytosis (GSK343) or chemotaxis (SB225002) suppressed organotropic colonization and significantly improved the survival of melanoma- bearing mice treated with immune checkpoint blockade (PD1 antibody). Conclusions: The heterogeneity of melanoma cells in utilization of tyrosine is associated with organotropic colonization, providing the basis for developing new strategies to combat melanoma.
format Online
Article
Text
id pubmed-8899568
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-88995682022-03-08 Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells Wang, Xuefeng Chen, Yu Lan, Bin Wang, Yu Lin, Wansong Jiang, Xu Ye, Jiayin Shang, Bingxue Feng, Chao Liu, Jun Zhai, Jingjie Xu, Muhan Li, Qing Lin, Liangyu Hu, Mingyuan Zheng, Fanjun Chen, Ling Shao, Changshun Wang, Ying Shi, Yufang Theranostics Research Paper Background: Dietary tyrosine regulating melanoma progression has been well-recognized. However, whether tyrosine-based melanin anabolism contributes to pulmonary and cerebral organotropic colonization of melanoma remains elusive. Furthermore, approaches based on targeting tyrosinase activity to inhibiting multi-organ metastasis of melanoma cells need to be designed and validated. Methods: Patients derived melanoma cells and mouse B16 melanoma cells with different pigmentation were employed in this investigation. Tyrosine content dynamics in tumors and multiple organs during the melanoma progression was monitored, and tyrosine-based melanin synthesis of melanoma cells derived from multi-organ was determined. Additionally, we also adopted RNA-seq, flow cytometry, real-time PCR and composite metastasis mouse model to analyze organotropic colonization and to validate designed therapeutic strategies. Results: B16 melanoma cells with high activity of tyrosinase and sensitivity of tyrosine utilization for melanin synthesis (Tyr-H cells) easily colonized in the lung, while B16 melanoma cells lacking above characteristics (Tyr-L cells) exhibited potent proliferation in the brain. Mechanistically, Tyr-H cells recruited and trained neutrophils and macrophages to establish pulmonary metastatic niche dependent on highly secreted CXCL1 and CXCL2 and an excessive melanosome accumulation-induced cell death. Tyr-L cells enhanced PD-L1 expression in tumor-infiltrated macrophages when they are progressing in the brain. Accordingly, intervention of tyrosinase activity (2-Ethoxybenzamide or hydroquinone) in combination with inhibitors of phagocytosis (GSK343) or chemotaxis (SB225002) suppressed organotropic colonization and significantly improved the survival of melanoma- bearing mice treated with immune checkpoint blockade (PD1 antibody). Conclusions: The heterogeneity of melanoma cells in utilization of tyrosine is associated with organotropic colonization, providing the basis for developing new strategies to combat melanoma. Ivyspring International Publisher 2022-01-31 /pmc/articles/PMC8899568/ /pubmed/35265199 http://dx.doi.org/10.7150/thno.69198 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Wang, Xuefeng
Chen, Yu
Lan, Bin
Wang, Yu
Lin, Wansong
Jiang, Xu
Ye, Jiayin
Shang, Bingxue
Feng, Chao
Liu, Jun
Zhai, Jingjie
Xu, Muhan
Li, Qing
Lin, Liangyu
Hu, Mingyuan
Zheng, Fanjun
Chen, Ling
Shao, Changshun
Wang, Ying
Shi, Yufang
Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells
title Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells
title_full Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells
title_fullStr Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells
title_full_unstemmed Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells
title_short Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells
title_sort heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899568/
https://www.ncbi.nlm.nih.gov/pubmed/35265199
http://dx.doi.org/10.7150/thno.69198
work_keys_str_mv AT wangxuefeng heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT chenyu heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT lanbin heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT wangyu heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT linwansong heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT jiangxu heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT yejiayin heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT shangbingxue heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT fengchao heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT liujun heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT zhaijingjie heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT xumuhan heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT liqing heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT linliangyu heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT humingyuan heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT zhengfanjun heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT chenling heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT shaochangshun heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT wangying heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells
AT shiyufang heterogeneityoftyrosinebasedmelaninanabolismregulatespulmonaryandcerebralorganotropiccolonizationmicroenvironmentofmelanomacells