Matrix metalloproteinase 9/gelatinase B is required for neural crest cell migration

Abstract

This study determined the role of MMP9/gelatinase B during the migration onset of Neural Crest Cells (NCC) in avian embryos. NCC are neuroepithelial progenitors that convert into mesenchyme and migrate along defined paths throughout the embryo. To engage in migration, NCC loose cell contacts, detach from the neural tube and invade the surrounding environment. Multiple signals and transcription factors that regulate these events have been identified. Nevertheless, little is known regarding effectors that act downstream to execute the actual NCC migration. Matrix metalloproteinases (MMPs) compose a large family of enzymes whose principal substrates are basement membranes, adhesion proteins and the extracellular matrix (ECM) components. A major subgroup of MMPs, the gelatinases (MMP9 and 2) are central to many adult physiological and pathological processes, such as tumor metastasis and angiogenesis, in which cell-cell and cell-matrix contacts are degraded to allow migration. As NCC undergo similar processes during development, we hypothesized that MMP9 may also promote the migration of NCC. MMP9 was found to be expressed in delaminating and migrating NCC of both cranial and trunk axial levels. Blocking MMP9 resulted in a dramatic inhibition of NCC delamination and migration, without perturbing specification or survival. This inhibition occurred at regions containing both premigratory and migrating cells, indicative for the central role of MMP9 in executing the detachment of NCC from the neural tube as well as their migration. Conversely, excess MMP9 enhanced mesenchymalization and delamination of NCC and accelerated progenitors to undergo precocious migration. Examination of the mechanistic activity of MMP9 revealed its capability to degrade the adhesion molecule N-cadherin as well as the basement-membrane protein laminin within or around NCC, respectively. Altogether, our study reveals MMP9 as a novel effector which is required for NCC delamination and migration.

HIF-2α as a prognostic marker for breast cancer progression and patient survival

“…To achieve metastasis, a tumor cell must disrupt cell-cell and cell-extracellular matrix contacts, migrate through stromal tissue, invade the basement membrane, and enter/exit the blood stream. These steps are primarily accomplished by the activity of the MMP family of enzymes (Singh et al, 2012;Monsonego-Ornan et al, 2012). However, we did not find that MMP-2 had prognostic importance in the multivariate Cox proportional hazard regression analysis.…”

Extracellular metalloproteinases in neural crest development and craniofacial morphogenesis

“…On the other hand, mmp-9 transcript was detected in all chick embryo NC cells and in the regions through which they migrate (Monsonego-Ornan et al, 2012). Loss of MMP-9 function by using either an MMP-9-selective inhibitor or an antisense morpholino decreased NC cell delamination and migration both in vitro and in vivo at multiple stages in this study, while addition of MMP-9 enhanced both delamination and migration.…”

Ophiopogonin-D suppresses MDA-MB-435 cell adhesion and invasion by inhibiting matrix metalloproteinase-9

“…Among these MMPs, MMP-2 (gelatinase-A) and MMP-9 (gelatinase-B) are mainly involved in cancer metastasis and invasion. They predominantly degrade gelatin and type IV, V, XI and XVI collagen, the major structural component of basement membrane, which appears to be crucial in tumor cell invasion and metastasis (8)(9)(10). A previous study reported that oroxylin A could inhibit migration and invasion of human breast MDA-MB-435 cancer cells via the inhibition of MMP-2 and MMP-9 (11).…”