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
5638 - Incidence of Vascular Thromboembolism Events in Cancer Patients Receiving Immunotherapy: A Single Institution Experience.
Presenter: Laura Gutiérrez Sainz
Session: Poster Display session 1
Resources:
Abstract
5182 - High Incidence of Venous Thromboembolic Events (VTE) in Patients with Diffuse Large B-Cell Lymphoma.
Presenter: Alaa Abufara
Session: Poster Display session 1
Resources:
Abstract
1504 - Weight Loss over Time in Non-Small Cell Lung Cancer: Results from a Landmark Analysis of 800+ Prospectively-Treated Patients
Presenter: Jennifer Le-rademacher
Session: Poster Display session 1
Resources:
Abstract
3972 - The prognostic significance of preoperative nutritional status in resected pancreatic ductal adenocarcinoma (PDAC).
Presenter: Salvatore Paiella
Session: Poster Display session 1
Resources:
Abstract
2313 - Impact of Timing and Technique of Gastrostomy Placement on the Outcome of Patients (pts) with Head and Neck Cancer (HNC)
Presenter: M Julia Lostes Bardaji
Session: Poster Display session 1
Resources:
Abstract
5219 - Clinical & nutritional determinants of quality of life in patients with incurable cancer
Presenter: Louise Daly
Session: Poster Display session 1
Resources:
Abstract
4075 - Loss of skeletal muscle mass during palliative chemotherapy is a poor prognostic factor in patients with advanced gastric cancer
Presenter: In Gyu Hwang
Session: Poster Display session 1
Resources:
Abstract
4159 - Impact of nutritional derangement on treatment outcome in advanced non-small-cell lung cancer (A-NSCLC) patients (pts).
Presenter: Ilaria Trestini
Session: Poster Display session 1
Resources:
Abstract
1210 - Sarcopenia and pretreatment anemia as prognostic factors for patients with localized muscle invasive bladder cancer treated by neoadjuvant chemotherapy and radical cystectomy
Presenter: Emilien Billon
Session: Poster Display session 1
Resources:
Abstract
2490 - Gender effect on the pharmacokinetics (PK) and pharmacodynamics (PD) of anamorelin (ANAM) in healthy volunteers and cancer patients with cachexia
Presenter: Stein Kaasa
Session: Poster Display session 1
Resources:
Abstract