title: WISP-1 contributes to fractionated irradiation-induced radioresistance in esophageal carcinoma cell lines and mice.
abstract: Cancer cells that survive fractionated irradiation can be radioresistant and cause tumor recurrence. However, the molecular mechanisms underlying the development of radioresistance in cancer cells remain elusive. The aim of this study was to investigate the role of WISP-1 in the development of radioresistance in esophageal carcinoma during fractionated irradiation. Radioresistant esophageal cancer cells were generated from normal esophageal cancer cells via fractionated irradiation, and expression levels of related proteins were determined by Western blot. Radiosensitivity of cells was established by clonogenic cell survival assays, and cell cycle distribution was evaluated by flow cytometry. Protein distributions were determined by immunofluorescence, and cell toxicity was evaluated by cell counting kit-8 assays. In vivo validations were performed in a xenograft transplantation mouse model. Our data indicate that WISP-1 plays an important role in the development of radioresistance in esophageal cancer cells during fractionated irradiation. The overexression of WISP-1 in esophageal cancer cells was associated with radioresistance. Depletion of extracellular WISP-1 by antibody neutralizing reversed radioresistance and directly induced mitotic catastrophe resulting in cell death. WISP-1 may be a candidate therapeutic target in the treatment of recurrent esophageal carcinoma after radiotherapy.
authors.affiliation: Department of Radiation Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory of Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Li
authors.affiliation: Division of PET/CT, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Zheng
authors.affiliation: Division of PET/CT, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D055511:CCN Intercellular Signaling Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics*; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism
chemical_list: D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; D017077:Culture Media, Conditioned; D011518:Proto-Oncogene Proteins; D051176:beta Catenin
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