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Induction of Matrix Metalloproteinase MMP‐9 (92‐kDa Gelatinase) by Retinoic Acid in Human Neuroblastoma SKNBE Cells
Author(s) -
ChambautGuérin AnneMarie,
Hérigault Sabine,
RouetBenzineb Patricia,
Rouher Caroline,
Lafuma Chantal
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.740508.x
Subject(s) - neurite , retinoic acid , gelatinase , matrix metalloproteinase , biology , zymography , nerve growth factor , immunocytochemistry , gelatinase a , microbiology and biotechnology , neuroblastoma , cellular differentiation , cell culture , chemistry , endocrinology , extracellular matrix , biochemistry , receptor , in vitro , genetics , gene
Retinoic acid (RA) has been shown to induce human neuroblastoma SKNBE cell differentiation into a neuronal phenotype. Whether this neuronal differentiation is associated with modulation of matrix gelatinase [matrix metalloproteinase (MMP)‐2 and MMP‐9] expression was investigated in SKNBE cell cultures exposed to RA for 14 days. Their differentiation into a neuronal phenotype was typified by neural cell adhesion molecule and growth‐associated protein‐43 expression. Gelatinase expression was assessed by gel zymography, quantitative RT‐PCR, and immunocytochemistry. Neuronal markers were located in neurites and ganglion‐like clusters of neuronal cells induced upon RA exposure. MMP‐2 expression was constitutive and remained unchanged at both the mRNA and protein levels in response to RA, tumor necrosis factor‐α (TNFα), or phorbol 12‐myristate 13‐acetate (PMA) treatment. In contrast, MMP‐9 was inducible by RA, TNFα, or PMA. MMP‐9 was progressively enhanced by RA as a function of time exposure until day 14. The addition of TNFα or PMA potentiated RA‐induced MMP‐9 expression with a synergic maximal effect at day 14 of RA exposure. Immunoreactive MMP‐9 was located early in outgrowing neurites, but only at day 14 of RA exposure in extensive neuritic networks. Taken together, the correlation between the MMP‐9 expression by SKNBE cells and the time scale of their differentiation into a neuronal phenotype allowed us to propose that MMP‐9 could participate in the neurite growth process and cell migration and organization into ganglion‐like clusters.