Details

Autor(en) / Beteiligte

• Harrington, Brittney S
• He, Yaowu
• Davies, Claire M
• Wallace, Sarah J
• Adams, Mark N
• Beaven, Elizabeth A
• Roche, Deborah K
• Kennedy, Catherine
• Chetty, Naven P
• Crandon, Alexander J
• Flatley, Christopher
• Oliveira, Niara B
• Shannon, Catherine M
• deFazio, Anna
• Tinker, Anna V
• Gilks, C Blake
• Gabrielli, Brian
• Brennan, Donal J
• Coward, Jermaine I
• Armes, Jane E
• Perrin, Lewis C
• Hooper, John D

Titel

Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer

Ist Teil von

• British journal of cancer, 2016-02, Vol.114 (4), p.417-426

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2016

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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.