Proteomics profiling of cholangiocarcinoma exosomes: A potential role of oncogenic protein transferring in cancer progression

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1852

Article

Dutta, Suman^1,2  Reamtong, Onrapak³  Panvongsa, Wittaya^2,4  Kitdumrongthum, Sarunya^2,4  Janpipatkul, Keatdamrong^1,2,5  Sangvanich, Polkit⁶  Piyachaturawat, Pawinee^1,2,4,7  Chairoungdua, Arthit^1,2,4 

[1] Mahidol Univ, Dept Physiol, Fac Sci, Bangkok 10400, Thailand

[2] Mahidol Univ, Res Ctr Transport Prot Med Innovat, Fac Sci, Bangkok 10400, Thailand

[3] Mahidol Univ, Fac Trop Med, Dept Mol Trop Med & Genet, Bangkok 10400, Thailand

[4] Mahidol Univ, Toxicol Grad Program, Fac Sci, Bangkok 10400, Thailand

[5] Navamindradhiraj Univ, Fac Med Vajira Hosp, Dept Basic Med Sci, Bangkok, Thailand

[6] Chulalongkorn Univ, Fac Sci, Dept Chem, Bangkok, Thailand

[7] Mahidol Univ, Chakri Naruebodindra Med Inst, Ramathibodi Hosp, Fac Med, Bangkok 10400, Thailand

关键词: Cholangiocarcinoma;    Exosomes;    Proteomics;    Invasion;    Migration;    Cell-cell communication;   

DOI  :  10.1016/j.bbadis.2015.06.024

来源: Elsevier

【 摘 要 】

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 beta-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. (C) 2015 Elsevier B.V. All rights reserved.

【 授权许可】

Free