JCP

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
[Advanced]

Journal of Clinical Pathology 2005;58:1242-1248; doi:10.1136/jcp.2004.025338
Copyright © 2005 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Add article to my folders
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tan, X
Right arrow Articles by Ogawa, M
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tan, X
Right arrow Articles by Ogawa, M

ORIGINAL ARTICLE

Involvement of MMP-7 in invasion of pancreatic cancer cells through activation of the EGFR mediated MEK–ERK signal transduction pathway

X Tan, H Egami, M Abe, F Nozawa, M Hirota, M Ogawa

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan

Correspondence to:
Dr H Egami
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan; tanxd{at}hotmail.com Aims: To clarify the involvement of matrix metalloproteinase-7 (MMP-7) in cell dissociation and the subsequent invasion of pancreatic cancer cells.

Methods: Western blotting, in vitro invasion assay, immunocytochemistry, and immunohistochemistry were performed in pancreatic cancer cell lines or pancreatic cancer tissue.

Results: The active form of the MMP-7 protein was expressed exclusively in the conditioned medium of dissociated (PC-1.0 and AsPC-1) pancreatic cancer cells, whereas proMMP-7 protein was only detected in the conditioned medium of non-dissociated (PC-1 and Capan-2) cells. Both intracellular and conditioned medium localised MMP-7 was greatly reduced by treatment with the epidermal growth factor receptor (EGFR) inhibitor AG1478 and the mitogen activated protein kinase kinase (MEK) inhibitor U0126 in pancreatic cancer cells. MMP-7 treatment significantly induced the disruption of tight junction (TJ) structures and subsequent cell dissociation, and activation of the EGFR mediated MEK– ERK (extracellular signal regulated protein kinase) signalling pathway in the non-dissociated pancreatic cancer cells. Moreover, the strong in vitro invasiveness of dissociated cells was inhibited by AG1478 and U0126 treatment, whereas the weak invasiveness of non-dissociated cells was apparently induced by MMP-7 treatment. In addition, MMP-7 expression was stronger at the invasive front than at the centre of human pancreatic tumours.

Conclusion: MMP-7 is involved in cell dissociation and the subsequent invasion of pancreatic cancer cells. It induces the disruption of TJ structures and forms a positive feedback loop with activation of the EGFR mediated MEK–ERK signalling pathway.


Abbreviations: EGFR, epidermal growth factor receptor; ERK, extracellular signal regulated protein kinase; FI, fluorescence intensity; MEK, mitogen activated protein kinase kinase; MMP-7, matrix metalloproteinase-7; p-, phosphorylated; TJ, tight junction; ZO-1, zonula occludens-1

Keywords: matrix metalloproteinase-7; invasion; signal transduction pathway; tight junction; pancreatic cancer




This article has been cited by other articles:


Home page
Ann. Surg. Oncol.Home page
M. M. Javle, J. F. Gibbs, K. K. Iwata, Y. Pak, P. Rutledge, J. Yu, J. D. Black, D. Tan, and T. Khoury
Epithelial-Mesenchymal Transition (EMT) and Activated Extracellular Signal-regulated Kinase (p-Erk) in Surgically Resected Pancreatic Cancer
Ann. Surg. Oncol., December 1, 2007; 14(12): 3527 - 3533.
[Abstract] [Full Text] [PDF]


Home page
Mol Cancer ResHome page
F.-q. Wang, Y. Smicun, N. Calluzzo, and D. A. Fishman
Inhibition of Matrilysin Expression by Antisense or RNA Interference Decreases Lysophosphatidic Acid-Induced Epithelial Ovarian Cancer Invasion
Mol. Cancer Res., November 1, 2006; 4(11): 831 - 841.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
K. J. Aitken, G. Block, A. Lorenzo, D. Herz, N. Sabha, O. Dessouki, F. Fung, M. Szybowska, L. Craig, and D. J. Bagli
Mechanotransduction of Extracellular Signal-Regulated Kinases 1 and 2 Mitogen-Activated Protein Kinase Activity in Smooth Muscle Is Dependent on the Extracellular Matrix and Regulated by Matrix Metalloproteinases
Am. J. Pathol., August 1, 2006; 169(2): 459 - 470.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
Journal of Clinical Pathology Molecular Pathology
Terms and conditions relating to subscriptions purchased online  ¦  Website terms and conditions  ¦  Privacy policy
Copyright © 2005 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists.