Plasmin: Its Role in the Extracellular Processing of Progalanin in Tumor Tissue
Galanin is a neuropeptide that is widely distributed in the central and peripheral nervous systems. In a previous study, we showed that a small cell lung carcinoma (SCLC) cell line, SBC-3A, released progalanin but not galanin, and that progalanin was then converted to galanin(1-20), the active form. Because the galanin(1-20) had undergone hydrolysis at Arg and Lys residues, the protease concerned was surmised to have a trypsin-like activity. The present study was performed to identify the trypsin-like protease which had previously been found to activate progalanin in this tumor tissue. The protease was isolated using chromatography and electrophoresis, and identified in tumor extracts from SBC-3A tumor- bearing mice; the major protease was found to be plasmin. We next confirmed that extracellular processing of progalanin occurs in SCLC tumor tissue (tumors produced by the implantation of SBC-3A cells into mice), and in two types of breast tumor tissue (obtained by implantation into mice of BT-549 and MDA-MB-436 cells). In cell culture, processed forms of progalanin were undetectable in SBC-3A, BT-549 or MDA-MB-436 cells. Conversely, gel filtration chromatography analysis of tumor extracts from SBC-3A, BT-549 and MDA-MB-436-bearing mice, revealed that galanin-like immunoreactivity (galanin-LI) in these tumor extracts was due to the presence of progalanin (14 kDa) and galanin(1-20) (2 kDa). Moreover, trypsin-like protease activity was elevated, and plasmin was expressed abundantly in SBC-3A, BT-549 and MDA-MB-436 tumors in mice. In addition, tranexamic acid, a plasmin inhibitor, inhibited progalanin conversion to galanin(1-20). The present study revealed that plasmin was present in tumor tissue, and that it was responsible for processing progalanin to galanin(1-20) in the extracellular environment.
No Supplementary Data
Document Type: Research Article
Publication date: 2011-12-01
More about this publication?
- Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.