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LOXL2 is required for EMT and migration in pancreas cancer

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Presentation on theme: "LOXL2 is required for EMT and migration in pancreas cancer"— Presentation transcript:

1 LOXL2 is required for EMT and migration in pancreas cancer
Yun Sun Lee,MS., Joon Seong Park,MD.,PhD., Dong Sup Yoon,MD., PhD. Pancreas-biliary Cancer Clinic, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul. Korea Good after noon everyone. My name is YunSun Lee. From yonsei university college of medicine. Today, I’ll talk about the role of LOXL2 in Pancreas cancer Emt and migration.

2 Introduction Pancreatic adenocarcinoma
- Has one of the highest mortality rates of any malignancy (Median survival 6~9 months, 5y survival rate ~5% ) - Complex, heterogenous and genetically unstable disease - Dense and desmoplastic stroma *Role of ECM Support tumor growth and promotes metastasis Physical barrier to drug delivery It is known that The median survival is only 6 to 9 months and 5 year survival rate is only about 5% , Pancreatic adenocarcinoma or pancreas cancer has the highest mortality rates of any malignancy. They show complex, heterogenous and genetically unstable features. Among them, we focused on the presence of a dense desmoplastic reaction that consist largely of fibroblasts, pancreatic stellate cells, and extracellular matrix proteins. Especially, ECM has important role to support tumor growth and metastasis promotion and construct the physical barrier to drug delivery.

3 Introduction Lysyl Oxidase-Like 2 (LOXL2)
- Extracellular enzymes responsible for crosslink formation in fibrillar collagen and elastin - Able to regulate the EMT markers Cell biology 2010

4 Material and Method Patients : 84 patients received radical resection for pancreas cancer from 2002 to 2012 at Gangnam Severance Hospital Post-adjuvant chemotherapy regimen (8 weeks after surgery, 6 Cycle of gemcitabine 1000mg/BSA) Cell lines : Miapaca2, Panc-1, AsPc1, BxPc3 Methods - IHC staining - siRNA transfection - Cell cytotoxicity (WST method) - RT-PCR & qPCR - Gel electrophoresis and Western blot -Transendothelial Migration assay and Invasion assay

5 LOXL2 expression in pancreas cancer and influence on EMT markers
MIA PaCa-2 PANC1 AsPC1 BxPC3 LOXL2 Snail (Exp.30m) CDH1 L1CAM β-actin LOXL2 Snail CDH1 P-FAK FAK P-SRC SRC L1CAM N-Cadherin Vimentin β-actin siCon siLOXL2 siCon siLOXL2 MIA PaCa PANC AsPC BxPC3 vc LOXL vc LOXL2 (L.E)

6 LOXL2 expression in pancreas cancer and influence on EMT markers
MIA PaCa PANC AsPC BxPC3 siCon siLOXL2 siCon siLOXL vc LOXL vc LOXL2 LOXL2 Snail CDH1 L1CAM GAPDH

7 Knockdown of LOXL2 induce the morphological change and inhibit the invasiveness of pancreas cancer
siControl siLOXL2 MIA PaCa-2 PANC1 MIA PaCa-2 PANC1 siControl siLOXL2 siControl siLOXL2 MIA PaCa-2 PANC1 siControl siLOXL2

8 Highly expressed LOXL2 observed in pancreas cancer patients and has correlation with recurrence and DFS rates Pancreas Tissue Normal Cancer LOXL2 antibody RT-PCR LOXL2 β-actin N T LOXL2 β-actin WB

9 Conclusion LOXL2 Pancreas Cancer LOXL2 overexpression induce EMT
Metastasis & invasiveness Poor prognosis LOXL2 Desmoplastic microenvironment is a hallmark feature in pancreas cancer The stromal EMT contribute aggressive progression by fostering tumor growth and metastatic spread also enhance the chemo-resistance Through the ECM modulation, LOXL2 can be the independent marker for metastatic disease and potentially be a valuable target for improvement of patient outcome and survival

10 Acknowledgement Thank you. -YunSun Lee -JoonSeong Park -DongSup Yoon
-SeungMyung Dong -JooHee Jung This is acknowledgement and thank you for listening. Thank you.

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