title: Proteomics profiling of cholangiocarcinoma exosomes: A potential role of oncogenic protein transferring in cancer progression.
abstract: Cholangiocarcinoma (CCA), a common primary malignant tumor of bile duct epithelia, is highly prevalent in Asian countries and unresponsive to chemotherapeutic drugs. Thus, a newly recognized biological entity for early diagnosis and treatment is highly needed. Exosomes are small membrane bound vesicles found in body fluids and released by most cell types including cancer cells. The vesicles contain specific subset of proteins and nucleic acids corresponding to cell types and play essential roles in pathophysiological processes. The present study aimed to assess the protein profiles of CCA-derived exosomes and their potential roles. We have isolated exosomes from CCA cells namely KKU-M213 and KKU-100 derived from Thai patients and their roles were investigated by incubation with normal human cholangiocyte (H69) cells. Exosomes were internalized into H69 cells and had no effects on viability or proliferation of the host cells. Interestingly, the exosomes from KKU-M213 cells only induced migration and invasion of H69 cells. Proteomic analysis of the exosomes from KKU-M213 cells disclosed multiple cancer related proteins that are not present in H69 exosomes. Consistent with the protein profile, treatment with KKU-M213 exosomes induced β-catenin and reduced E-cadherin expressions in H69 cells. Collectively, our results suggest that a direct cell-to-cell transfer of oncogenic proteins via exosomal pathway may be a novel mechanism for CCA progression and metastasis.
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Research Center of Transport Proteins for Medical Innovation, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Suman
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Onrapak
authors.initials: O
authors.lastname: Reamtong
authors.affiliation: Research Center of Transport Proteins for Medical Innovation, Faculty of Science, Mahidol University, Bangkok, Thailand; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Wittaya
authors.initials: W
authors.lastname: Panvongsa
authors.affiliation: Research Center of Transport Proteins for Medical Innovation, Faculty of Science, Mahidol University, Bangkok, Thailand; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Sarunya
authors.initials: S
authors.lastname: Kitdumrongthum
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Research Center of Transport Proteins for Medical Innovation, Faculty of Science, Mahidol University, Bangkok, Thailand; Department of Basic Medical Science, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand.
authors.forename: Keatdamrong
authors.initials: K
authors.lastname: Janpipatkul
authors.affiliation: Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Polkit
authors.initials: P
authors.lastname: Sangvanich
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Research Center of Transport Proteins for Medical Innovation, Faculty of Science, Mahidol University, Bangkok, Thailand; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand; Chakri Naruebodindra Medical Institute, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pawinee
authors.initials: P
authors.lastname: Piyachaturawat
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Research Center of Transport Proteins for Medical Innovation, Faculty of Science, Mahidol University, Bangkok, Thailand; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address: arthit.chi@mahidol.ac.th.
authors.forename: Arthit
authors.initials: A
authors.lastname: Chairoungdua
keywords: Cell–cell communication; Cholangiocarcinoma; Exosomes; Invasion; Migration; Proteomics