title: Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer.
abstract: BACKGROUND
  Syndecan-1 (Sdc-1) shedding induced by matrix metalloproteinase-7 (MMP-7) and additional proteases has an important role in cancer development. However, the impact of Sdc-1 shedding on chemotherapeutic resistance has not been reported.
  
  
  METHODS
  We examined Sdc-1 shedding in colorectal cancer by enzyme-linked immunosorbent assay (ELISA), Dot blot, reverse transcription-PCR (RT-PCR), immunohistochemistry and so on, its impact on chemotherapeutic sensitivity by collagen gel droplet embedded culture-drug sensitivity test (CD-DST) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), and potential mechanisms of action by Dot blot, western blot and immunofluorescence.
  
  
  RESULTS
  Sdc-1 shedding was increased in colorectal cancer patients, Sdc-1 serum levels in postoperative patients were lower than in preoperative patients, but still higher than those observed in healthy adults. Patients with high preoperative Sdc-1 serum levels were less responsive to 5-Fluorouracil, Oxaliplatin, Irintecan, Cisplatin or Paclitaxel chemotherapy. Moreover, the disease-free survival of patients with high preoperative Sdc-1 serum levels was significantly poorer. The possible mechanism of chemotherapy resistance in colorectal cancer can be attributed to Sdc-1 shedding, which enhances EGFR phosphorylation and downstream signalling.
  
  
  CONCLUSIONS
  Shed Sdc-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer, and Sdc-1 serum levels could be a new prognostic marker in colorectal cancer.
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Gastrointestinal Oncology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Clinical Laboratory, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: D
authors.initials: D
authors.lastname: Zuo
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Digestive Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Medicine, Tianjin Chest Hospital, Tianjin 300000, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Gastrointestinal Oncology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Hepatology and Infectious Disease, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Clinical Laboratory, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: L
authors.initials: L
authors.lastname: Ren
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Gastrointestinal Oncology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Gastrointestinal Oncology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: T
authors.initials: T
authors.lastname: Deng
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Digestive Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Cancer Cell Biology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: G
authors.initials: G
authors.lastname: Ying
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Gastrointestinal Oncology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ba
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D000077146:Irinotecan; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053668:Syndecan-1; D000077150:Oxaliplatin; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin