Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer

• Published in: British journal of cancer Vol. 111; no. 10; pp. 1965 - 1976
• Main Authors: Wang, X, Zuo, D, Chen, Y, Li, W, Liu, R, He, Y, Ren, L, Zhou, L, Deng, T, Ying, G, Ba, Y
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-11-2014; Nature Publishing Group
• Subjects: 631/154/53/2422; 692/4028/67/1059/99; 692/699/67/1059/2326; 692/699/67/1504/1885; Aged; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Biopsy; Blotting, Western; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Cancer Research; Case-Control Studies; Cell growth; Cell Proliferation - drug effects; Chemotherapy; Cisplatin - administration & dosage; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Disease prevention; Drug Resistance; Drug Resistance, Neoplasm; Epidemiology; Female; Flow Cytometry; Fluorescent Antibody Technique; Fluorouracil - administration & dosage; Gastroenterology. Liver. Pancreas. Abdomen; Growth factors; Hospitals; Humans; Immunoenzyme Techniques; Laboratories; Larynx; Male; Matrix Metalloproteinase 7 - metabolism; Medical prognosis; Medical research; Medical sciences; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Oncology; Organoplatinum Compounds - administration & dosage; Paclitaxel - administration & dosage; Patients; Real-Time Polymerase Chain Reaction; Receptor, Epidermal Growth Factor - metabolism; Research centers; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Small Interfering - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Syndecan-1 - antagonists & inhibitors; Syndecan-1 - genetics; Syndecan-1 - metabolism; Translational Therapeutics; Tumor Cells, Cultured; Tumors; China; colorectal cancer; syndecan-1; HB-EGF; chemotherapy; Rectal disease; Colorectal cancer; Syndecan 1; Malignant tumor; Epidermal growth factor receptor; Colonic disease; Resistance; Chemotherapy; Treatment; Cancerology; Heparin-binding epidermal growth factor-like growth factor; Digestive diseases; Intestinal disease; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.493

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.