Overexpression of MMP-9 Contributes to Invasiveness of Prostate Cancer Cell Line LNCaP

Abstract

Matrix metallaprotinase-9 (MMP-9) is zinc-containing proteinase whose expression and trafficking are frequently altered in cancer. MMP-9 in the plasma membrane and the secreted forms are thought to contribute to the invasive and metastatic properties of malignant tumors. We have manipulated the expression of MMP-9 in prostate tumor cell line LNCaP and measured their capacity to invade through a basement membrane matrix. Stable expression of human MMP-9 in a poorly metastatic LNCaP prostate cancer cell line produced a 2-3-fold increase in MMP-9 activity and a comparable increase in invasiveness. Transient transfection of LNCaP stable clone expressing MMP-9 with MMP-9 antisense oligonucleotide (ASODN) produced 55–90% less MMP-9 than control cells and were proportionately less invasive. In contrast, manipulating MMP-9 levels had no effect on cell migration across an uncoated membrane. A standard MMP-9 inhibitor at a concentration ranging from 1–10 nM, caused a nearly quantitative inhibition of extracellular MMP-9 activity and had significant effect on basement membrane invasion. Collectively, these results confirm the role of MMP-9 in tissue remodeling associated with prostate tumor invasion.

• Cancer invasion
• Prostate cancer
• Metalloproteinases
• MMP-9
• Tissue re-modeling
• Metastasis
• Proteases

ACKNOWLEDGEMENT

The authors thank Mr. Ramnik Chawda (Deceased), Division of Allergy Immunology and Rheumatology, Department of Medicine, State University of New York at Buffalo, Buffalo, NY 14203 for technical assistance. This work was supported by the Margaret Duffy and Robert Cameron Troup Memorial Fund for Cancer Research of the Kaleida Health System, Buffalo, NY.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.