Increased ratio of vascular endothelial growth factor to semaphorin3A is a negative prognostic factor in human meningiomas

Barresi, Valeria; Tuccari, Giovanni

doi:10.1111/j.1440-1789.2010.01105.x

Cited by 38 publications

(25 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The elevated levels of VEGF seen in this study confirm earlier reports not only on benign meningiomas, but atypical and malignant ones as well (40). It has been suggested that the increased ratio of the pro-angiogenesis factor VEGF to the anti-angiogenic factor SEMASA (which is expressed in human meningiomas association with low microvessel density) is a negative predictor of recurrence in these neoplasms (41). EMMPRIN, the extracellular MMP inducer, was also very highly expressed in all the meningiomas.…”

Section: Discussionsupporting

confidence: 80%

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Rooprai

Martin

King

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.

show abstract

Section: Discussionsupporting

confidence: 80%

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Rooprai

Martin

King

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…120 Sema3A also functions as a potent inhibitor of angiogenesis and tumor progression in many types of solid tumors. Down-regulation of sema3A expression in tumor cells promotes tumor angiogenesis and tumor progression in many types of solid tumors [121][122][123][124][125][125][126][127] suggesting that it functions as an endogenous negative regulator of the angiogenic switch. 128 Prolonged stimulation of endothelial cells with sema3A induces apoptosis of endothelial cells suggesting that induction of apoptosis is a part of the mechanism by which it inhibits angiogenesis.…”

Section: Semaphorins As Regulators Of Tumor Progressionmentioning

confidence: 99%

The role of the semaphorins in cancer

Neufeld

Mumblat

Smolkin

et al. 2016

Cell Adhesion & Migration

View full text Add to dashboard Cite

The semaphorins were initially characterized as axon guidance factors, but have subsequently been implicated also in the regulation of immune responses, angiogenesis, organ formation, and a variety of additional physiological and developmental functions. The semaphorin family contains more then 20 genes divided into 7 subfamilies, all of which contain the signature sema domain. The semaphorins transduce signals by binding to receptors belonging to the neuropilin or plexin families. Additional receptors which form complexes with these primary semaphorin receptors are also frequently involved in semaphorin signaling. Recent evidence suggests that semaphorins also fulfill important roles in the etiology of multiple forms of cancer. Some semaphorins have been found to function as bona-fide tumor suppressors and to inhibit tumor progression by various mechanisms while other semaphorins function as inducers and promoters of tumor progression. The semaphorin familyThe semaphorin family members are divided into 8 subclasses of which subclasses 1 and 2 contain invertebrate semaphorins while subclasses 3-7 contain the 22 vertebrate semaphorins. The 8th subclass contains viral semaphorins. In early publications, semaphorins were assigned confusing names. This situation was rectified by the adoption of a unified nomenclature in which sema is followed by the subclass number and by alphabetic designation within the subclass.1 Semaphorins are characterized by the presence of a »500 amino-acids long sema domain located close to their N-termini which is also present in semaphorin receptors of the plexin family, and by a plexin-semaphorin-integrin (PSI) domain located downstream to the sema domain. The sema domain is essential for semaphorin activity and plays a role in the determination of the receptor binding specificity.2 The sema domains of several different semaphorins were characterized by X-ray crystallography revealing a b propeller topology.3-5 Different semaphorin subclasses are characterized by class specific structural motifs. Thus, the vertebrate semaphorins belonging to classes 3, 4 and 7 contain immunoglobulin like domains, class-5 semaphorins contain thrombospondin repeats and class-3 semaphorins contain a basic domain. Class-3 semaphorins are the only vertebrate semaphorins produced as secreted proteins while other vertebrate semaphorins are membrane anchored or trans-membrane proteins that can be further processed into soluble forms by proteolytic cleavage (Fig.

show abstract

“…1,25,51,52 Semaphorin3A (SEMA3A) is a negative regulator of neoangiogenesis, the formation of blood vessels from endothelial progenitors. 53,54 A high concentration of intra-tumoral neoangiogenesis, indicated by a high microvessel density (MVD), is significantly correlated with shorter overall survival and decreased recurrence-free survival. [54][55][56][57] High VEGF/SEMA3A ratio is strongly associated with an increase in recurrence, proliferation index, and higher histological grades, 54 as grade III meningiomas demonstrate a 10-fold increase in VEGF-A relative to benign meningiomas.…”

Section: Prognostic Factorsmentioning

confidence: 99%

Chromosomal alterations, prognostic factors, and targeted molecular therapies for malignant meningiomas

Yew

Trang

Nagasawa

et al. 2013

Journal of Clinical Neuroscience

View full text Add to dashboard Cite

Increased ratio of vascular endothelial growth factor to semaphorin3A is a negative prognostic factor in human meningiomas

Cited by 38 publications

References 44 publications

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

The role of the semaphorins in cancer

Chromosomal alterations, prognostic factors, and targeted molecular therapies for malignant meningiomas

Contact Info

Product

Resources

About