title: Targeting chemotherapy-induced PTX3 in tumor stroma to prevent the progression of drug-resistant cancers.
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.
authors.affiliation: Institute of Basic Medical Science, National Cheng Kung University, Tainan, Taiwan R.O.C.
authors.forename: Jhih-Ying
authors.initials: JY
authors.lastname: Chi
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan R.O.C.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Hsiao
authors.affiliation: Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan R.O.C.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan R.O.C.
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Lo
authors.affiliation: Cancer Center and Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan R.O.C.
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan R.O.C.
authors.forename: Jhen-Yi
authors.initials: JY
authors.lastname: Hong
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan R.O.C.
authors.forename: Yang-Ming
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan R.O.C.
authors.forename: Xiu
authors.initials: X
authors.lastname: Han
authors.affiliation: Institute of Basic Medical Science, National Cheng Kung University, Tainan, Taiwan R.O.C.
authors.forename: Shao-Ming
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan R.O.C.
authors.forename: Ben-Kuen
authors.initials: BK
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research and Translational Center for Glandular Malignancies, National Health Research Institutes, Tainan, Taiwan R.O.C.
authors.forename: Kelvin K
authors.initials: KK
authors.lastname: Tsai
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan R.O.C.|Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan R.O.C.
authors.forename: Ju-Ming
authors.initials: JM
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002945:Cisplatin / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000737:chemistry; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005472:Fluorouracil / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D058628:Myofibroblasts / Q000187:drug effects; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000683:Serum Amyloid P-Component / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000187:drug effects; D000099153:Pentraxins
chemical_list: D000970:Antineoplastic Agents; D002097:C-Reactive Protein; D051743:CCAAT-Enhancer-Binding Protein-delta; D002945:Cisplatin; D017077:Culture Media, Conditioned; D005472:Fluorouracil; D010446:Peptide Fragments; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C000609609:pentraxin 3 (200-236)
keywords: CAFs; CEBPD; PTX3; TAMs; tumor microenvironment