50P - Functional role of 4F2hc in pancreatic ductal adenocarcinoma

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Cancer biology
Basic Scientific Principles
Presenter Daniela Bianconi
Citation Annals of Oncology (2016) 27 (6): 1-14. 10.1093/annonc/mdw362
Authors D. Bianconi1, M. Herac2, A. Gleiss3, M. Unseld1, R. Weigl1, M. Schindl4, W. Scheithauer1, C. Zielinski1, G. Prager1
  • 1Internal Medicine I, Oncology, Vienna General Hospital (AKH) - Medizinische Universität Wien, 1090 - Vienna/AT
  • 2Klinisches Institut Für Pathologie, Vienna General Hospital (AKH) - Medizinische Universität Wien, 1090 - Vienna/AT
  • 3Institut Für Klinische Biometrie, Cemsiis, Vienna General Hospital (AKH) - Medizinische Universität Wien, 1090 - Vienna/AT
  • 4Universitätsklinik Für Chirurgie, Vienna General Hospital (AKH) - Medizinische Universität Wien, 1090 - Vienna/AT

Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive cancers with limited prognosis. With less than 5 % five-year-overall survival, the characterization of new therapeutic targets is urgently needed. 4F2hc is a cell surface-antigen overexpressed in some tumor cells and therefore, it represents a promising novel therapeutic target. In the current study, we investigated the functional role of 4F2hc in PDAC.

Methods

4F2hc protein expression level was analyzed in human pancreatic cancer tissue (222 cases) and matched adjacent tissue (141 cases) via immunohistochemistry (IHC). Additionally, pancreatic cancer cells were isolated from fresh human tumor tissue and 4F2hc+ cells were phenotypically analyzed via flow cytometry. To characterize the functional role of 4F2hc in PDAC, 4F2hc was downregulated in pancreatic cancer cell lines by lentiviral transduction and in vitro experiments were performed.

Results

Using IHC, we demonstrated that 4F2hc is aberrantly expressed in PDAC and matched adjacent tissue. However, there was no significant difference in 4F2hc expression in the different grades and stages. Although Kaplan-Meier survival curves and Cox analyses did not revealed a significant association between 4F2hc expression and OS, we observed a trend that suggests an association between absence of 4F2hc expression and prolonged survival. Additionally, our results showed that 4F2hc+ cells isolated from fresh tumor tissue co-expressed other known markers of PDAC such as MUC4 and MUC1.To determine the role of 4F2hc in PDAC, cell behavior between 4F2hc+ cells and 4F2hc low expressing cells was compared. We found that 4F2hc downregulation significantly inhibited tumorsphere formation and cell proliferation by arresting cell cycle.

Conclusions

Herein, we demonstrated that 4F2hc is overexpressed in resected tumor tissue as well as in matched adjacent tissue of patients with pancreatic cancer. Moreover, our data suggests that 4F2hc expression increases tumorigenesis by enhancing cell proliferation and promoting anchorage-independent growth in vitro. Although further studies are needed, our results suggest that 4F2hc might be a novel therapeutic target of PDAC.

Clinical trial identification

Legal entity responsible for the study

Medical University of Vienna

Funding

Medical University of Vienna

Disclosure

All authors have declared no conflicts of interest.