Matrix Gla protein is a vitamin K-dependent protein secreted by chondrocytes and vascular smooth muscle cells. The presence of matrix Gla protein was reported in arterial and venous walls, lungs, kidney, uterus, heart, tooth cementum and eyes. Several studies identified matrix Gla protein in tumoral pathology.Until recently, it was thought to only have an inhibitory role of physiological and ectopic calcification. New studies demonstrated that it also has a role in physiological and pathological angiogenesis, as well as in tumorigenesis.The aim of this review is to report the latest findings related to the expression and clinical implications of matrix Gla protein in different types of cancer with an emphasis on cerebral tumors.

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Calcified meningiomas have a slower growth rate and a better outcome than non-calcified meningiomas. Matrix Gla Protein (MGP) acts as an inhibitor of soft tissue calcification. Depending on its carboxylation status MGP may occur in two conformations: uncarboxylated (ucMGP) or carboxylated (cMGP). Low levels of serum ucMGP have been described to be a sign of tissue calcification. In calcified tumoral tissue samples we identified both ucMGP (r = 0.957, p[0.001) and cMGP (r = 1, p[0.001), while non-calcified tumors were negative for both MGP conformation deposits. The concentration of serum t-ucMGP in patients with calcified and non-calcified meningiomas were not significantly different (3499�1388 vs. 3882�2558).

Meningiomas are classified by the World Health Organization (WHO) in three grades, based on morphological features. Independent of this grading, the presence of calcification in meningiomas influences their growth rate. The messenger RNA of matrix Gla protein (MGP), an extra-hepatic protein with different conformations involved in the homeostasis of ectopic calcification has been found in meningiomas and was shown to be regulated in breast cancer by miR-155-5p, a specific micro RNA. Therefore, we investigated the expression of miR-155-5p and its relationship with local MGP conformations in different grade meningiomas. According to the WHO classification, our 41 samples of meningiomas were stratified in groups WHO I and WHO II. Using real time polymerase chain reaction, we observed a higher miR-155-5p expression in group WHO I versus group WHO II [with a fold change (FC) of 3.83, p=0.027)]. Moreover, the expression of miR-155-5p was higher in calcified tumors compared to non-calcified tumors in all samples (FC=3.01, p=0.047) and in group WHO I (FC=3.65, p=0.048). Utilizing immunohistochemistry, we determined the concurrent presence of all MGP conformations in calcified meningiomas. This study was the first to establish higher miR-155-5p expression in grade WHO I and calcified meningiomas, which could improve molecular classification and targeted therapy and also the presence of all MGP conformations in calcified meningiomas, confirming the existence of an anti-calcification mechanism in meningiomas..