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

Jhih Ying Chi, Yu Wei Hsiao, Chien Feng Li, Yu Chih Lo, Zu Yau Lin, Jhen Yi Hong, Yang Ming Liu, Xiu Han, Shao Ming Wang, Ben Kuen Chen, Kelvin K. Tsai, Ju Ming Wang

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)23987-24001
Number of pages15
JournalOncotarget
Volume6
Issue number27
DOIs
Publication statusPublished - 2015 Jan 1

All Science Journal Classification (ASJC) codes

  • Oncology

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