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

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. and Hooper, John D. (2016) Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer. British Journal of Cancer, 114 4: 417-426. doi:10.1038/bjc.2015.471

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Author 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.
Title Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer
Journal name British Journal of Cancer   Check publisher's open access policy
ISSN 0007-0920
Publication date 2016-02-16
Year available 2016
Sub-type Article (original research)
DOI 10.1038/bjc.2015.471
Open Access Status File (Publisher version)
Volume 114
Issue 4
Start page 417
End page 426
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted abstract
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.
Keyword CDCP1
CUB-domain containing protein 1
High-grade serous ovarian cancer
Patient-derived xenograft
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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