@article {Tan1242, author = {X Tan and H Egami and M Abe and F Nozawa and M Hirota and M Ogawa}, title = {Involvement of MMP-7 in invasion of pancreatic cancer cells through activation of the EGFR mediated MEK{\textendash}ERK signal transduction pathway}, volume = {58}, number = {12}, pages = {1242--1248}, year = {2005}, doi = {10.1136/jcp.2004.025338}, publisher = {BMJ Publishing Group}, abstract = {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{\textendash} 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{\textendash}ERK signalling pathway.}, issn = {0021-9746}, URL = {https://jcp.bmj.com/content/58/12/1242}, eprint = {https://jcp.bmj.com/content/58/12/1242.full.pdf}, journal = {Journal of Clinical Pathology} }