This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ravanko, K. Articles by Hölttä, E. Search for Related Content PubMed PubMed Citation Articles by Ravanko, K. Articles by Hölttä, E.

Cysteine Cathepsins Are Central Contributors of Invasion by Cultured Adenosylmethionine Decarboxylase-Transformed Rodent Fibroblasts

¹ Department of Pathology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; and ² Institute of Biotechnology, University of Helsinki, Helsinki, Finland

Adenosylmethionine decarboxylase (AdoMetDC), a key enzyme in the biosynthesis of polyamines, is often up-regulated in cancers. We have demonstrated previously that overexpression of AdoMetDC alone is sufficient to transform NIH 3T3 cells and induce highly invasive tumors in nude mice. Here, we studied the transformation-specific alterations in gene expression induced by AdoMetDC by using cDNA microarray and two-dimensional electrophoresis technologies. We specifically tried to identify the secreted proteins contributing to the high invasive activity of the AdoMetDC-transformed cells. We found a significant increase in the expression and secretion of procathepsin L, which was cleaved and activated in the presence of glycosaminoglycans (heparin), and a smaller increase in cathepsin B. Inhibition of the cathepsin L and B activity by specific peptide inhibitors abrogated the invasive capacity of the AdoMetDC transformants in Matrigel. The transformed cells also showed a small increase in the activity of gelatin-degrading matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator activities, neither of which was sensitive to the inhibitors of cathepsin L and B. Furthermore, the invasive potency of the transformed cells remained unaffected by specific inhibitors of MMPs. The results suggest that cysteine cathepsins are the main proteases contributing to the high invasiveness of the AdoMetDC-transformed cells and that the invasion potential is largely independent of activation of the MMPs.

This article has been cited by other articles:

				H. B. Schiller, A. Szekeres, B. R. Binder, H. Stockinger, and V. Leksa Mannose 6-Phosphate/Insulin-like Growth Factor 2 Receptor Limits Cell Invasion by Controlling {alpha}V{beta}3 Integrin Expression and Proteolytic Processing of Urokinase-type Plasminogen Activator Receptor Mol. Biol. Cell, February 1, 2009; 20(3): 745 - 756. [Abstract] [Full Text] [PDF]

				C. Yao, J. E. Donelson, and M. E. Wilson Internal and Surface-Localized Major Surface Proteases of Leishmania spp. and Their Differential Release from Promastigotes Eukaryot. Cell, October 1, 2007; 6(10): 1905 - 1912. [Abstract] [Full Text] [PDF]

				P. Nummela, M. Yin, M. Kielosto, V. Leaner, M. J. Birrer, and E. Holtta Thymosin {beta}4 Is a Determinant of the Transformed Phenotype and Invasiveness of S-Adenosylmethionine Decarboxylase-Transfected Fibroblasts Cancer Res., January 15, 2006; 66(2): 701 - 712. [Abstract] [Full Text] [PDF]

				A. C. Borczuk, H. K. Kim, H. A. Yegen, R. A. Friedman, and C. A. Powell Lung Adenocarcinoma Global Profiling Identifies Type II Transforming Growth Factor-{beta} Receptor as a Repressor of Invasiveness Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 729 - 737. [Abstract] [Full Text] [PDF]