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Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers

The tumor microenvironment has been suggested to participate in tumorigenesis, but the nature of the communication between cancer cells and the microenvironment, especially in response to anticancer drugs, remains obscure. We determined that activation of the CCAAT/enhancer binding protein delta (CE...

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Autores principales: Chi, Jhih-Ying, Hsiao, Yu-Wei, Li, Chien-Feng, Lo, Yu-Chih, Lin, Zu-Yau, Hong, Jhen-Yi, Liu, Yang-Ming, Han, Xiu, Wang, Shao-Ming, Chen, Ben-Kuen, Tsai, Kelvin K., Wang, Ju-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695165/
https://www.ncbi.nlm.nih.gov/pubmed/26124179
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author Chi, Jhih-Ying
Hsiao, Yu-Wei
Li, Chien-Feng
Lo, Yu-Chih
Lin, Zu-Yau
Hong, Jhen-Yi
Liu, Yang-Ming
Han, Xiu
Wang, Shao-Ming
Chen, Ben-Kuen
Tsai, Kelvin K.
Wang, Ju-Ming
author_facet Chi, Jhih-Ying
Hsiao, Yu-Wei
Li, Chien-Feng
Lo, Yu-Chih
Lin, Zu-Yau
Hong, Jhen-Yi
Liu, Yang-Ming
Han, Xiu
Wang, Shao-Ming
Chen, Ben-Kuen
Tsai, Kelvin K.
Wang, Ju-Ming
author_sort Chi, Jhih-Ying
collection PubMed
description The tumor microenvironment has been suggested to participate in tumorigenesis, but the nature of the communication between cancer cells and the microenvironment, especially in response to anticancer drugs, remains obscure. We determined that activation of the CCAAT/enhancer binding protein delta (CEBPD) response to Cisplatin and 5-Fluorouracil in cancer-associated macrophages and fibroblasts contributed to the metastasis, invasion, acquired chemoresistance and stemness of cancer cells by in vitro and in vivo assays. Specifically, reporter and in vivo DNA binding assays were used to determine that Pentraxin 3 (PTX3) is a CEBPD responsive gene and serves a protumor role upon anticancer drug treatment. Finally, a PTX3 peptide inhibitor RI37 was developed and assessed the antitumor effects by in vivo assays. RI37 could function as a promising inhibitor for preventing cancer progression and the metastasis, invasion and progression of drug-resistant cancers. The identification of PTX3 provided a new insight in the interaction between host and tumor and the RI37 peptide showed a great opportunity to largely reduce the risk of invasion and metastasis of cancer and drug-resistant cancers.
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spelling pubmed-46951652016-01-26 Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers Chi, Jhih-Ying Hsiao, Yu-Wei Li, Chien-Feng Lo, Yu-Chih Lin, Zu-Yau Hong, Jhen-Yi Liu, Yang-Ming Han, Xiu Wang, Shao-Ming Chen, Ben-Kuen Tsai, Kelvin K. Wang, Ju-Ming Oncotarget Research Paper The tumor microenvironment has been suggested to participate in tumorigenesis, but the nature of the communication between cancer cells and the microenvironment, especially in response to anticancer drugs, remains obscure. We determined that activation of the CCAAT/enhancer binding protein delta (CEBPD) response to Cisplatin and 5-Fluorouracil in cancer-associated macrophages and fibroblasts contributed to the metastasis, invasion, acquired chemoresistance and stemness of cancer cells by in vitro and in vivo assays. Specifically, reporter and in vivo DNA binding assays were used to determine that Pentraxin 3 (PTX3) is a CEBPD responsive gene and serves a protumor role upon anticancer drug treatment. Finally, a PTX3 peptide inhibitor RI37 was developed and assessed the antitumor effects by in vivo assays. RI37 could function as a promising inhibitor for preventing cancer progression and the metastasis, invasion and progression of drug-resistant cancers. The identification of PTX3 provided a new insight in the interaction between host and tumor and the RI37 peptide showed a great opportunity to largely reduce the risk of invasion and metastasis of cancer and drug-resistant cancers. Impact Journals LLC 2015-06-08 /pmc/articles/PMC4695165/ /pubmed/26124179 Text en Copyright: © 2015 Chi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chi, Jhih-Ying
Hsiao, Yu-Wei
Li, Chien-Feng
Lo, Yu-Chih
Lin, Zu-Yau
Hong, Jhen-Yi
Liu, Yang-Ming
Han, Xiu
Wang, Shao-Ming
Chen, Ben-Kuen
Tsai, Kelvin K.
Wang, Ju-Ming
Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers
title Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers
title_full Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers
title_fullStr Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers
title_full_unstemmed Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers
title_short Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers
title_sort targeting chemotherapy-induced ptx3 in tumor stroma to prevent the progression of drug-resistant cancers
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695165/
https://www.ncbi.nlm.nih.gov/pubmed/26124179
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