Retinoic acid stimulates meningioma cell adhesion to the extracellular matrix and inhibits invasion

Meningiomas are tumours derived from the arachnoid and pia mater. During em bryogenesis, these membranes develop from the migrating craniofacial neural crest. We have previously demonstrated that meningiomas have characteristi c features of embryonic meninges. Craniofacial neural crest derivatives are affected during normal development and migration by retinoic acid. We spec ulated, therefore, that meningioma cell migration and invasion would be aff ected in a similar way. In this study we investigated the mechanisms of inv asion and migration in meningiomas and the effects of retinoic acid (RA). W e found that low doses of RA inhibit in vitro invasion in meningioma cells, without affecting cell proliferation or viability. The matrix metalloprote inases MMP-2 (72 kDa gelatinase) and MMP-9 (92 kDa gelatinase), which play a key role in invasion in other tumours, are not affected by RA. RA inhibit s cell migration on collagen I and fibronectin. A possible mechanism for th ese effects is provided by the fact that RA strongly stimulates adhesion of meningioma cells to extracellular matrix substrates. As in vitro invasion, migration and decreased adhesion to the extracellular matrix correlate wit h the clinical manifestation of tumour invasion, we conclude that RA induce s a non-invasive phenotype in meningioma cells. (C) 1999 Cancer Research Ca mpaign.