Meizothrombin, an intermediate of prothrombin cleavage potently activates renal carcinoma cells by interaction with PAR-type thrombin receptors.
Recently, meizothrombin (MT), an intermediate enzyme in the prothrombin cleavage cascade has been shown to activate cells of a brain tumor cell line by interaction with PAR-1-type thrombin receptors with a potency comparable to that of thrombin. In this study, we investigated the effect of recombinant human MT (rMT) on calcium mobilization in primary cultures established from surgically resected human renal cell carcinomas. Meizothrombin induced very rapidly transient calcium mobilization in RCC cells comparable to that observed with thrombin. RCC cells stimulated with thrombin after rMT challenge were unable to elicit a new calcium response and vice versa. Therefore, rMT and thrombin seem to activate calcium signaling in primary RCC cultures by similar mechanisms including PAR-1- and PAR-3-type thrombin receptors as shown by using PAR-type specific antibodies. Our results demonstrate rMT as a potent activator of human RCC cells suggesting a function of not only thrombin but also of this catalytically active thrombin precursor enzyme in human renal cell carcinoma.
Kaufmann
R
R
Research Laboratory, Department of General and Visceral Surgery, Institute of Immunology, Medical Faculty at the Friedrich Schiller University Jena, Research Center Lobeda, Germany. roland.kaufmann@med.uni-jena.de
Junker
U
U
Schilli-Westermann
M
M
Klötzer
C
C
Scheele
J
J
Junker
K
K
D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D004792:Enzyme Precursors / Q000378:metabolism / Q000494:pharmacology*; D004950:Esterases / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000502:physiology; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000378:metabolism*; D011994:Recombinant Proteins; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004792:Enzyme Precursors; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; C105295:protease-activated receptor 3; D011516:Prothrombin; D004950:Esterases; D013917:Thrombin; C026812:meizothrombin; D002118:Calcium