Tumour metabolites regulate tissue kallikrein in human umbilical vein endothelial cells.
Angiogenesis, the sprouting of new blood vessels, is tightly mediated via a myriad of endogenous factors. A pro-angiogenic alteration facilitates the formation of neovascular tumour networks, thereby providing mechanisms for uncontrolled growth. The kallikrein-kinin system is postulated to be pro-angiogenic since its components have been detected in both endothelial cells and tumour tissue. No studies have, however, focussed on the role of tissue kallikrein (TK) in human angiogenic endothelial cell-tumour interactions. This study has optimised a challenge model whereby endothelial cells are presented with neuroblastoma metabolites, and vice versa. Image analysis of immunoreactive TK revealed a dose-dependant, significant reduction of TK localisation within endothelial cells, while gene expression remained unchanged, the latter determined by in situ RT-PCR. Neuroblastoma cells, when challenged with endothelial cell metabolites, displayed no change in TK synthesis or localisation. Alterations in TK synthesis and/or storage by angiogenic endothelial cells may be mediated by tumour-released signals and possibly indicate a shift from a proteolytic to a mitogenic function of TK. The challenge model provides a relatively simple experimental system to study angiogenic factors in tumour-endothelial cell interaction, and is the first to localise both TK and its mRNA within angiogenic endothelial and tumour cells.
Naidoo
S
S
Department of Clinical and Experimental Pharmacology, Nelson R Mandela School of Medicine, Private Bag 7, Congella 4013, Durban, South Africa. naidoot@nu.ac.za
Raidoo
D
D
Mahabeer
R
R
McLean
M
M
D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D013363:Submandibular Gland / Q000166:cytology / Q000378:metabolism
D007610:Kallikreins