PO-230 Cysteine-rich secretory protein 3 regulates progression from in situ to invasive prostate cancer
Year: 2018
Type: conference-abstract
Abstract: Introduction One of the most challenging aspects of prostate cancer diagnosis is predicting whether cancer will remain indolent or progress to invasive, aggressive and potentially lethal disease. Current markers such as PSA are unreliable and tumours requiring treatment may remain undetected while others are over-treated. Cysteine-rich secretory protein 3 (CRISP3) is a member of a poorly defined family of proteins that is highly up-regulated in human prostate cancer. Material and methods We sought to define the role of CRISP3 in the molecular pathology of prostate cancer through the generation of a Crisp3 knockout mouse line, which was crossed onto the Hi-MYC mouse model of prostatic adenocarcinoma. The pro-invasive actions of CRISP3 were also studied using human and mouse derived cell lines and purified recombinant CRISP3. Results and discussions Here we show that CRISP3 induces migration and invasion of prostate cancer cells in vitro. Furthermore, and consistent with human expression data, CRISP3 was dramatically up-regulated with advanced disease in the Hi-MYC mouse model of prostatic adenocarcinoma and specifically associated with transformed and migratory cells both in vivo and in vitro. Importantly, Crisp3 deletion delayed the transition from prostatic intraepithelial neoplasia to carcinoma in situ and blocked the transition to the invasive disease. These effects are attributed to changes in the expression of EMT markers in response to CRISP3. We are currently validating potential CRISP3 binding partners identified by mass spectrometry. Conclusion Collectively, these data define CRISP3 as pro-tumourigenic in the prostate through a role in promoting cancer invasion.
Source: ESMO Open
Authors: M. Volpert, J. Hu, R. Rebello, M. O’Bryan, L. Furic
Institutions: Monash University, Peter MacCallum Cancer Centre
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,910
OpenAlex ID: W2809980558