Avtor/Urednik		Premzl, Aleš
Naslov		Vpliv monoklonskih protiteles proti katepsin B in proteinaznih inhibitorjev na proliferacijo, invazijo in angiogenezo tumorskih celic in vitro
Prevedeni naslov		The effects of anti-cathepsin B monoclonal antibodies and proteinase inhibitors on tumor cell proliferation, invasion and angiogenesis in vitro
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Medicinska fakulteta
Leto izdaje		2001
Obseg		str. 79
Jezik		slo
Abstrakt		Lysosomal cysteine proteinases cathepsins B and L and aspartic proteinase cathepsin D are associated with the processes of tumor progression. The proteolytic activity of cathepsin B has been suggested to facilitate degradation of extracellular matrix, leading to invasion, metastasis and tumor angiogenesis. Several natural and synthetic proteinase inhibitors have not provided, expected antitumor activity in vivo, probably due to insufficient specificity and high toxicity. Monoclonal antibodies neutralizing enzyme activity are more specific and less toxic compared to the inhibitors and may serve as alternative agents. Fusing mouse splenocytes and mieloma cells we prepared neutralizing monoclonal antibody, which is capable to bind an epitope near the active site of cathepsin B, and to inhibit in vitro its proteolytic activity against fluorogenic substrates Z-Arg-Arg-AMC and BODIPY FL casein. Its inhibitory effect was tested also on tumor cell viability, proliferation and invasion and compared to several natural and synthetic inhibitors of cysteine and aspartic proteinases. For this purpose MCF-l0A neoT transformed human breast epithelial cells were used, expressing cathepsins B, L and D as detected by immunofluorescence microscopy. Monoclonal antibody significantly decreased invasion (47.3 +- 0.3 % at 0.5 microM, whereas no effect on cell viability and proliferation was detected in the same concentration range. Among cysteine proteinase inhibitors, the most effective was chicken cystatin (82.8 ž 1.0%, 2 N,M), the next was E-64 (56.5 f 1.3%, 10 N,M). Both generai inhibitors of cysteine proteinases showed higher inhibition compared to cathepsin L specific inhibitor CLIK-148, (32.7 microM 1.5%, 10 microM. (Abstract truncated at 2000 characters)
Deskriptorji		CATHEPSIN B ANTIBODIES, MONOCLONAL TUMOR CELLS, CULTURED CYSTEINE PROTEINASE INHIBITORS ASPARTIC PROTEINASES NEOVASCULARIZATION, PATHOLOGIC HYBRIDOMAS CELL COUNT CELL SURVIVAL