Differential regulation of gelatinase b and tissue‐type plasminogen activator expression in human bowes melanoma cells

Abstract

A comparison of the production of tissue-type plasminogen activator (t-PA) and gelatinases A and B was made at the mRNA and protein levels in human Bowes melanoma cells treated with phorbol myristate acetate (PMA). Immunocytochemical analysis confirmed previous quantitative data on PMA-mediated induction of t-PA. It also showed that t-PA immunoreactivity can be restrained to the local environment of the producing cell, most probably by interaction with extracellular matrix components. Zymographical analysis showed that gelatinase B protein was induced by PMA, whereas gelatinase A remained at the constitutive level. Protein kinase C (PKC) appeared to be involved in this regulation since, after PMA treatment (1) the PKC activity was found to be translocated from the cytosol to the particulate fraction of the cells and (2) addition of staurosporine and H-7 blocked the gelatinase B increase. Northern-blot hybridization showed a transient rise in t-PA and gelatinase B mRNA levels whereas gelatinase A mRNA levels remained unchanged. When c-fos and c-jun mRNAs were investigated, only that of c-fos was affected by PMA. Activation by PMA can be kinetically ordered as follows: translocation of PKC to the membrane fraction, transcription of the c-fos gene and eclipsing of gelatinase B mRNA, increase in steady-state mRNA levels of t-PA and gelatinase B and, finally, secretion of t-PA and gelatinase B glycoproteins. Our data also suggest that various proteases that are known to cooperate in the remodeling of the extracellular matrix can be differently regulated in one tumor-cell type.

Tumor necrosis factor α (TNFα) induces pro‐matrix metalloproteinase 9 production in human uterine cervical fibroblasts but interleukin 1 α antagonizes the inductive effect of TNFα

“…Recent studies have indicated that expression of proMMP-9 is regulated by PKC pathway in tumor cells [18,19] and T-lymphocytes [20,21]. In cervical fibroblasts, TNFc~ induced the production of proMMP-3 through PKC pathway as previous paper by Brenner et al [22].…”

Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion

“…The regulation of the expression and activity of MMP-9 is more complex than that of most other MMPs (Dubois et al, 1999). MMP-9 is not produced constitutively by most cells (Collier et al, 1988), but its activity is induced by different stimuli depending on the cell type (Houde et al, 1993), thereby providing a means of increasing its activity in response to specific pathophysiological events. Glioblastomas express greater amounts of MMPs than do either low-grade gliomas or normal brain in vivo (Rao et al, 1993;Forsyth et al, 1998;Yamamoto et al, 1996), and the activity of MMP-9 in particular in surgical specimens was proportional to the grade of the glioma .…”

Quercetin and sulforaphane in combination suppress the progression of melanoma through the down-regulation of matrix metalloproteinase-9

“…The regulation of MMP-9 activation is more complex than that of other mmps, as most cells in general do not express the constitutively active form of MMP-9. Rather, its activity is induced by different stimuli depending on cell type, thereby contributing to specific pathological events (21,22). Previous reports have demonstrated that transgenic mice lacking MMP-9 exhibit reduced keratinocyte hyperproliferation and a decreased incidence of invasive tumors (23).…”