Research Papers:
Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 2214 views | HTML 3295 views | ?
Abstract
Jhih-Ying Chi1, Yu-Wei Hsiao2, Chien-Feng Li3, Yu-Chih Lo2, Zu-Yau Lin4, Jhen-Yi Hong2, Yang-Ming Liu2, Xiu Han2, Shao-Ming Wang1, Ben-Kuen Chen2, Kelvin K. Tsai5 and Ju-Ming Wang2,6
1 Institute of Basic Medical Science, National Cheng Kung University, Tainan, Taiwan R.O.C.
2 Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan R.O.C.
3 Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan R.O.C.
4 Cancer Center and Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan R.O.C.
5 National Institute of Cancer Research and Translational Center for Glandular Malignancies, National Health Research Institutes, Tainan, Taiwan R.O.C.
6 Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan R.O.C.
Correspondence to:
Ju-Ming Wang, email:
Keywords: CEBPD, PTX3, TAMs, CAFs, tumor microenvironment
Received: February 25, 2015 Accepted: May 30, 2015 Published: June 08, 2015
Abstract
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 4364