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Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma

Cancer-associated fibroblasts (CAFs) are believed to influence tumor behavior and clinical outcomes. We previously showed that conditioned medium (CM) from CAFs induces proliferation and motility of esophageal squamous cell carcinoma (ESCC) cells. Here, we investigated the molecular mechanisms by wh...

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Autores principales: Tian, Baoqing, Chen, Xiaojia, Zhang, Huihua, Li, Xiaoyan, Wang, Jiakang, Han, Wei, Zhang, Li-Yi, Fu, Li, Li, Yan, Nie, Changjun, Zhao, Ying, Tan, Xuan, Wang, Hailong, Guan, Xin-Yuan, Hong, An
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522068/
https://www.ncbi.nlm.nih.gov/pubmed/28404945
http://dx.doi.org/10.18632/oncotarget.15857
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author Tian, Baoqing
Chen, Xiaojia
Zhang, Huihua
Li, Xiaoyan
Wang, Jiakang
Han, Wei
Zhang, Li-Yi
Fu, Li
Li, Yan
Nie, Changjun
Zhao, Ying
Tan, Xuan
Wang, Hailong
Guan, Xin-Yuan
Hong, An
author_facet Tian, Baoqing
Chen, Xiaojia
Zhang, Huihua
Li, Xiaoyan
Wang, Jiakang
Han, Wei
Zhang, Li-Yi
Fu, Li
Li, Yan
Nie, Changjun
Zhao, Ying
Tan, Xuan
Wang, Hailong
Guan, Xin-Yuan
Hong, An
author_sort Tian, Baoqing
collection PubMed
description Cancer-associated fibroblasts (CAFs) are believed to influence tumor behavior and clinical outcomes. We previously showed that conditioned medium (CM) from CAFs induces proliferation and motility of esophageal squamous cell carcinoma (ESCC) cells. Here, we investigated the molecular mechanisms by which the CAF-secreted proteins induce ESCC development and progression. Using antibody arrays, we identified urokinase plasminogen activator (uPA) as one of the main proteins whose release was increased in CAFs compared to normal fibroblasts (NFs). Immunohistochemical analysis of pathological sections showed that uPA-positive cells were localized at the boundaries of tumor and stroma tissues, in stroma between tumor nests, and within the tumors. Increased stromal uPA levels (132/146 cases) correlated with tumor invasion (p < 0.05) and overall survival of ESCC patients (p < 0.05). In vitro assays showed that uPA promotes ESCC cell proliferation, migration, and invasion via PI3K/AKT and ERK signaling pathways. In vivo, anti-uPA antibody suppressed tumor growth in ESCC xenografts. These results suggest that uPA released from stroma, and especially from CAFs, might be a predictive marker for ESCC diagnosis and prognosis, as well as an effective therapeutic target.
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spelling pubmed-55220682017-08-08 Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma Tian, Baoqing Chen, Xiaojia Zhang, Huihua Li, Xiaoyan Wang, Jiakang Han, Wei Zhang, Li-Yi Fu, Li Li, Yan Nie, Changjun Zhao, Ying Tan, Xuan Wang, Hailong Guan, Xin-Yuan Hong, An Oncotarget Research Paper Cancer-associated fibroblasts (CAFs) are believed to influence tumor behavior and clinical outcomes. We previously showed that conditioned medium (CM) from CAFs induces proliferation and motility of esophageal squamous cell carcinoma (ESCC) cells. Here, we investigated the molecular mechanisms by which the CAF-secreted proteins induce ESCC development and progression. Using antibody arrays, we identified urokinase plasminogen activator (uPA) as one of the main proteins whose release was increased in CAFs compared to normal fibroblasts (NFs). Immunohistochemical analysis of pathological sections showed that uPA-positive cells were localized at the boundaries of tumor and stroma tissues, in stroma between tumor nests, and within the tumors. Increased stromal uPA levels (132/146 cases) correlated with tumor invasion (p < 0.05) and overall survival of ESCC patients (p < 0.05). In vitro assays showed that uPA promotes ESCC cell proliferation, migration, and invasion via PI3K/AKT and ERK signaling pathways. In vivo, anti-uPA antibody suppressed tumor growth in ESCC xenografts. These results suggest that uPA released from stroma, and especially from CAFs, might be a predictive marker for ESCC diagnosis and prognosis, as well as an effective therapeutic target. Impact Journals LLC 2017-03-02 /pmc/articles/PMC5522068/ /pubmed/28404945 http://dx.doi.org/10.18632/oncotarget.15857 Text en Copyright: © 2017 Tian et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Tian, Baoqing
Chen, Xiaojia
Zhang, Huihua
Li, Xiaoyan
Wang, Jiakang
Han, Wei
Zhang, Li-Yi
Fu, Li
Li, Yan
Nie, Changjun
Zhao, Ying
Tan, Xuan
Wang, Hailong
Guan, Xin-Yuan
Hong, An
Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma
title Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma
title_full Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma
title_fullStr Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma
title_full_unstemmed Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma
title_short Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma
title_sort urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via pi3k/akt and erk signaling in esophageal squamous cell carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522068/
https://www.ncbi.nlm.nih.gov/pubmed/28404945
http://dx.doi.org/10.18632/oncotarget.15857
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