Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer
| Autor: | Anna V. Tinker, Donal J. Brennan, Mark N. Adams, Jermaine Coward, Catherine Kennedy, Niara Oliveira, Brittney S. Harrington, Christopher Flatley, Elizabeth A Beaven, Claire M. Davies, Naven Chetty, Anna deFazio, Catherine Shannon, Yaowu He, Deborah K Roche, Brian Gabrielli, Jane E. Armes, A.J. Crandon, C. Blake Gilks, John D. Hooper, Lewis Perrin, S J Wallace |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Pathology medicine.medical_specialty patient-derived xenograft CDCP1 SKOV3 CUB-domain containing protein 1 Mice 03 medical and health sciences 0302 clinical medicine Antigens CD Antigens Neoplasm Cell Movement Cell Line Tumor high-grade serous ovarian cancer Biomarkers Tumor medicine Animals Humans Neoplasm RNA Small Interfering Cell Proliferation Ovarian Neoplasms Cell growth business.industry Cancer medicine.disease Survival Analysis Cystadenocarcinoma Serous Neoplasm Proteins 3. Good health Disease Models Animal 030104 developmental biology Oncology 030220 oncology & carcinogenesis Monoclonal Cancer research Heterografts Immunohistochemistry Female Neoplasm Grading Translational Therapeutics Ovarian cancer business Cell Adhesion Molecules Clear cell |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2015.471 |
| Popis: | Background: Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer. Methods: CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis. Results: Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1-mediated activation of Src was observed in cultured cells and mouse xenografts. Conclusions: CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer. |
| Databáze: | OpenAIRE |
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