Abstract 3210
Background
Pancreatic cancer (PC) is a refractory disease and we have not an effective therapeutic strategy yet. Therefore, the development of a new therapeutic procedure is urgently required. Recently, protein tyrosine phosphatase (PTP) has been attracted as a new therapeutic target for some types of cancers. However, the biological significance of PTP in PC has never been elucidated yet. In the present study, to develop effective therapeutic strategy for refractory PC, the biological significance of PTP non-receptor type 3 (PTPN3) in PC is investigated.
Methods
Three pancreatic ductal adenocarcinoma cell (PDAC) lines were used as target cells. Inhibition or overexpression of PTPN3 was performed using PTPN3 siRNA/shRNA and plasmid, respectively. Protein expression was analyzed by western blot and immunostaining. Proliferation assay was performed by MTT assay. Migration and invasion were estimated by time-lapse imaging and matrigel invasion assay. Mice xenograft experiments were performed using BALB/c nude mice. Twenty-three surgically resected human PC specimens were used for immunostaining.
Results
1) PTPN3 is highly expressed in PC cells compared to that in normal pancreatic duct cells by immunostaining. 2) Inhibition of PTPN3 significantly decreased migration and invasion in PDAC through inhibition of epithelial mesenchymal transition (EMT) and matrix metalloproteinase (MMP)-2 expression. 3) PTPN3 inhibition significantly decreased proliferation in vitro in PDAC. 4) PTPN3 overexpression led to increased proliferation, migration and invasion in PDAC. 5) Tumor volume in mice injected with PTPN3-inhibited PDAC was significantly lower than that in control mice. The expressions of Ki-67 and VEGF in PTPN3-inhibited PDAC were lower than those in control. 6) Signaling from PTPN3 was through PI3K and MAPK signaling pathways. 7) When intensity of PTPN3 expression was divided into 2 groups; weak and strong, intensity of PTPN3 expression was positively correlated with tumor size (T factor) and clinical staging.
Conclusions
These results suggest that PTPN3 contributes to the induction of malignant phenotypes of pancreatic cancer and that PTPN3 could be a new effective and specific therapeutic target for PC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Kyushu University Hospital, Cancer Therapy and Research.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5189 - Association between serum HGF levels and neutrophil counts in small cell lung cancer and their impact on survival
Presenter: Laura Moliner
Session: Poster Display session 1
Resources:
Abstract
3539 - Prognostic role of RLF/MYCL1 and circPVT1 in SCLC.
Presenter: Clelia Tiziana Storlazzi
Session: Poster Display session 1
Resources:
Abstract
3438 - High-biologically effective dose radiotherapy improve the survival of small cell lung cancer patients with brain metastases: a propensity-matching analysis
Presenter: Qingyang Zhuang
Session: Poster Display session 1
Resources:
Abstract
3232 - Phase 1 open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of ABBV-181 and rovalpituzumab tesirine (ROVA-T) in patients with small cell lung cancer
Presenter: Emiliano Calvo
Session: Poster Display session 1
Resources:
Abstract
3633 - Activity of the novel Aurora kinase B inhibitor AZD2811 in biomarker-defined models of small cell lung cancer
Presenter: Carminia Maria Della Corte
Session: Poster Display session 1
Resources:
Abstract
3745 - Multi-level proteomics identifies FABP5 as a primary chemoresistance mediator in extensive-stage small cell lung cancer
Presenter: Yamei Chen
Session: Poster Display session 1
Resources:
Abstract
5049 - CLEPSIDRA trial: a pilot, biomarker-guided study to assess safety, tolerability, dose finding and efficacy of iadademstat in combination with platinum-etoposide in patients with relapsed, extensive-stage small cell lung cancer
Presenter: Alejandro Navarro Mendivil
Session: Poster Display session 1
Resources:
Abstract
5997 - Phased Avelumab combined with chemotherapy as first-line treatment for patients with advanced small-cell lung cancer (SCLC): The PAVE study, a Hellenic Cooperative Oncology Group Study
Presenter: Helena Linardou
Session: Poster Display session 1
Resources:
Abstract
4502 - Tobacco use in lung cáncer (LC) patients (p) in Spain
Presenter: Enric Carcereny Costa
Session: Poster Display session 1
Resources:
Abstract
4369 - Biomarker testing of lung cancer in Spain
Presenter: Delvys Rodriguez Abreu
Session: Poster Display session 1
Resources:
Abstract