Plasmin: its role in the extracellular processing of progalanin in tumor tissue.

Abstract

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.

• Authors: Hiroyuki Yamamoto, Shinta Ben, Shun Saitoh, Kengo Kamata, Kazuaki Iguchi, Minoru Hoshino
• Journal: Protein and peptide letters (Protein Pept Lett) Vol. 18 Issue 12 Pg. 1204-11 (Dec 2011) ISSN: 1875-5305 [Electronic] Netherlands
• PMID: 21707521 (Publication Type: Journal Article)

Chemical References

• trypsin-like serine protease
• Galanin
• Serine Endopeptidases
• Fibrinolysin

Topics

• Animals
• Blotting, Western
• Cell Line, Tumor
• Electrophoresis, Gel, Two-Dimensional
• Fibrinolysin (genetics, metabolism)
• Galanin (genetics, metabolism)
• Humans
• Lung Neoplasms (genetics, metabolism)
• Mice
• Radioimmunoassay
• Reverse Transcriptase Polymerase Chain Reaction
• Serine Endopeptidases (genetics, metabolism)
• Small Cell Lung Carcinoma (genetics, metabolism)