title: Influence of interferon-α on the expression of the cancer stem cell markers in pancreatic carcinoma cells.
abstract: The cytokine interferon-α (IFNα) belongs to the group of type I interferons already used in cancer therapy. This drug possesses radio- and chemo-sensitizing, and shows anti-angiogenic properties. Cancer stem cells (CSC) are a unique population of tumor cells that initiate secondary tumors, and are responsible for metastasis formation. Patients with pancreatic ductal adenocarcinoma (PDAC) have an especially poor prognosis, with 5-year survival rates of only ~1% and median survival of 4-6 months. PDAC is characterized by the presence of CSC. In this work we demonstrate for the first time that IFNα up-regulates the expression of the CSC markers CD24, CD44 and CD133 in in vitro and in vivo models of PDAC. We showed the IFNα effects on the migration and invasion of PDAC cells, which is associated with the level of the CSC marker expression. In vivo, this drug inhibits tumor growth but promotes metastasis formation in the early stage of tumor growth. We propose that IFNα may enhance the enrichment of CSC in PDAC tumors. Additionally we also suggest that in combination therapy of solid tumors with IFNα, this drug should be given to patients prior to chemotherapy to achieve the CSC activation.
authors.affiliation: Cell Transplantation Center, Research Institute for Organ Transplantation, Sichuan Academy of Medical Science & Sichuan Provincial People׳s Hospital, Chengdu, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Karakhanova
authors.affiliation: Cell Transplantation Center, Research Institute for Organ Transplantation, Sichuan Academy of Medical Science & Sichuan Provincial People׳s Hospital, Chengdu, China.
authors.forename: Xiaolun
authors.initials: X
authors.lastname: Huang
authors.affiliation: Cell Transplantation Center, Research Institute for Organ Transplantation, Sichuan Academy of Medical Science & Sichuan Provincial People׳s Hospital, Chengdu, China.
authors.forename: Shao Ping
authors.initials: SP
authors.lastname: Deng
authors.affiliation: Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
authors.affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany; Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Munich, Germany. Electronic address: alexandr.bazhin@med.uni-heidelberg.de.
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Bazhin
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D016898:Interferon-alpha
keywords: CD133; CD24; CD44; Orthotopic mouse tumor model; Pancreatic cancer