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

Abstract

Meningiomas are tumours derived from the arachnoid and pia mater. During embryogenesis, these membranes develop from the migrating craniofacial neural crest. We have previously demonstrated that meningiomas have characteristic features of embryonic meninges. Craniofacial neural crest derivatives are affected during normal development and migration by retinoic acid. We speculated, therefore, that meningioma cell migration and invasion would be affected in a similar way. In this study we investigated the mechanisms of invasion and migration in meningiomas and the effects of retinoic acid (RA). We found that low doses of RA inhibit in vitro invasion in meningioma cells, without affecting cell proliferation or viability. The matrix metalloproteinases 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 inhibits cell migration on collagen I and fibronectin. A possible mechanism for these 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 with the clinical manifestation of tumour invasion, we conclude that RA induces a non-invasive phenotype in meningioma cells. © 1999 Cancer Research Campaign

Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation

“…Although inactive as an inhibitor of SCLC cell proliferation, RA abrogated the invasive potential of these cell lines however. In line with these observations, it has been reported that RA inhibits the invasive potential of human meningiomas and melanoma cell lines without modifying their proliferation rate (23,27,43). Besides inhibiting invasion, RA increased the expression of trkA and p75 NGF receptors in NCI-N-592 and GLC8 cells and prevented the decrease of NGF receptors occurring during NGF withdrawal.…”

Beneficial effects of retinoic acid on extracellular matrix degradation and attachment behaviour in follicular thyroid carcinoma cell lines

“…In vitro data suggest that retinoids inhibit tumour invasion. This has been observed in prostate and other carcinomas , Vo et al 1998, Benbow et al 1999, meningioma (Pereda et al 1999) and melanoma (Hendrix et al 1990). One of the explanations may be decreased activity of uPA or tPA or enhanced expression of TIMPs (Hendrix et al 1990.…”

High Levels of Matrix Metalloproteinases Regulate Proliferation and Hormone Secretion in Pituitary Cells1

“…We also measured the levels of TIMP-1 protein in conditioned media from normal human pituitary and pituitary adenomas by ELISA. For comparison we selected aggressive tumor types known to express high levels of MMPs similar to those produced by pituitary adenomas (28). We found that most of the pituitary adenomas express relatively low or undetectable levels of TIMP-1 compared to aggressive cancer cells (Fig.…”

“…TIMP-1 was measured by ELISA as previously described (28). Biotrack ELISA systems specific for human TIMP-1 were purchased from Amersham Pharmacia Biotech (Aylesbury, UK).…”

“…Gelatinolytic activity was analyzed as previously described (24,28), using 10% polyacrylamide gels containing 0.2% gels. Conditioned media, obtained as described above, was mixed with loading buffer containing 2.5% SDS and incubated for 30 min at room temperature before loading into the gel.…”