Cloned cytolytic T-effector cells and their malignant variants produce an extracellular matrix degrading trypsin-like serine proteinase.
This report describes the distribution of a trypsin-like proteinase in defined homogeneous cytolytic T-cell lines (CTLL) and their in vitro and in vivo derived malignant T-lymphoma variants. By means of chromogenic peptide substrates, we found the enzyme to attack preferentially at the carboxy terminus of arginine, in particular when non-polar amino acids were present in the amino terminal neighbouring position. The enzyme was identified by means of various inhibitors as a serine type proteinase having a pH optimum around 8 X 5. Affinity chromatography in connection with molecular sieving resulted in a 200-fold purification and indicated a molecular weight (MW) of about 50,000 for the proteinase. The enzyme was found to be highly expressed in antigen-specific CTLL as well as in their tumorigenic variants. Both intact lymphocytes of all CTLL tested and Triton X-100 lysates or enriched proteinase preparations thereof were able to degrade a high molecular weight protein (casein) and to release high molecular weight split products from the sulphated proteoglycans in subendothelial extracellular matrix. The results are discussed with respect to the invasiveness of normal and malignant T lymphocytes and the proteinase is suggested to be crucially involved in the process of cellular migration in vivo.
D000818:Animals; D002364:Caseins / Q000378:metabolism; D002460:Cell Line; D010450:Endopeptidases / Q000096:biosynthesis*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D008223:Lymphoma / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D011509:Proteoglycans / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012697:Serine Endopeptidases; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology*
D002364:Caseins; D011509:Proteoglycans; D011948:Receptors, Antigen, T-Cell; D010450:Endopeptidases; D012697:Serine Endopeptidases