Induction of morphological differentiation of human neuroblastoma cells is accompanied by induction of tissue‐type plasminogen activator

Abstract

Human SH-SY5Y neuroblastoma cells treated with retinoic acid, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or nerve growth factor differentiated morphologically to neuronlike cells with increased amounts of neurofilament protein and mRNA. All three effectors induced an increase in the amount of relative molecular weight (Mr) 70,000 tissue-type plasminogen activator (t-PA) and its mRNA, as determined by immunocapture, enzyme activity, and Northern blotting analyses. About 90% of the t-PA activity was secreted to the culture medium. In contrast, of the three effectors studied, only TPA induced transcription of the proto-oncogene c-fos, studied as a control gene responsive to various stimuli, and induced a rapid increase in urokinase-type PA (u-PA). Most of the u-PA activity induced by TPA remained cell-associated. Because induction of differentiation correlated closely with induction of t-PA, and not u-PA, the authors propose that t-PA may have a functional role in the morphological differentiation of neuronal cells.

Up-regulation of urokinase-type plasminogen activator in squamous cell carcinoma of human larynx

“…In all cases examined, neoplastic cells expressed uPA mRNA (Figure 4) Rijken and Collen, 1981;Neuman et al, 1989).…”

Transcriptional and posttranscriptional regulation of the plasminogen activator system

“…Of neoplastic cells, tPAmay be produced by melanoma,neuroblastoma,ovarian cancer,breast cancer and pancreaticc ancer cells (63)(64)(65). Twom ajor regulatoryr egions have beenc haracterizedi nt he human, mouse and ratt PA promoters.…”

Morphological differentiation of human SH-SY5Y neuroblastoma cells inhibits human immunodeficiency virus type 1 infection

“…NGF treatment was less effective, because by 2 days elongated neurites were seen in only 20 to 30% of the cells (Table 1). In our previous study (Neuman et al, 1989) we have shown that treatment of SH-SY5Y cells with RA, 12-D-tetradecanoyl phorbol-13-acetate or NGF enhances production of mRNA for the 200K neurofilament protein. In the present study, we monitored the protein expression and performed immunofluorescent staining of the 160K to 200K neurofilament complex in SH-SY5Y cells with a polyclonal antibody specific for the complex (Vesanen et al, 1992).…”