Reversion-Inducing Cysteine-Rich Protein With Kazal Motifs (RECK) In Angiogenesis


Reversion-Inducing Cysteine-Rich Protein With Kazal Motifs (RECK) In Angiogenesis

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) may play a role in tumor angiogenesis. Glioblastomas, the most malignant type of primary brain tumor, are highly vascularized. Little is known about the role of RECK in angiogenesis of glioblastomas. The aims of this study were to characterize RECK expression and investigate the role of RECK in glioblastomas

Tumor samples from 50 patients with glioblastoma and brain tissue samples from neurologically normal controls were immunohistochemically stained for RECK, CD34, and vascular endothelial growth factor (VEGF). RECK was expressed in endothelial cells but not tumor cells. A significant correlation between microvessel density (MVD) according to RECK and CD34 was revealed. However, RECK expression was remarkably weak in glomeruloid vessels. MVD according to RECK staining was significantly lower than MVDto CD34 staining in the group with glomeruloid vascular proliferation, which was related with high expression of VEGF.

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) was first identified as a cDNA clone, the encoded protein of which induces morphological reversion (‘flat reversion’) in NIH3T3 cells transformed with the v-K-ras oncogene . In addition, RECK acts as a membrane-anchored metalloproteinase regulator and negatively regulates matrix metalloproteinase family members (e.g., MMP-2, MMP-9, and MT1-MMP), which contribute to tumor growth, invasion, angiogenesis, and metastasis . RECK mRNA is expressed ubiquitously in normal human tissues [5], but RECK is down regulated in many types of solid tumors. Down regulation of RECK often correlates with poor prognosis and recurrence of tumors.


On the other hand, RECK was known as having the function of angiogenesis. Oh et al. reported that embryos of RECK-deficient mice have severe developmental defects in the vascular network . In tumor models in which HT1080 cells and human umbilical vein endothelial cells are transfected with RECK siRNA, the vessel density and tumor weight are significantly lower compared with control tumor models. This result suggested that RECK induction in vascular endothelial cells is required for tumor growth [8]. Positive RECK staining is also seen in endothelial cells of human neuroblastomas and osteosarcomas, indicating the role in tumor angiogenesis. Chandana et al. reported that large and irregular dilated vessels are present in Reckinactivated mice, suggesting that Reck may play a role in intussusception and pruning rather than sprouting angiogenesis. Recent study has found that RECK modulates Wnt signaling pathways that acts in endothelial cells during angiogenesis in the central nervous system.


Glioblastomas are highly vascularized and the most aggressive type of malignant glioma. Despite adequate surgical treatment, radiation, and chemotherapy, tumors often recur, and the prognosis is quite poor. Few reports have examined the role of RECK in gliomas. The RECK expression profile in gliomas is not known. Our study reported that RECK is expressed in endothelial cells in gliomas and that microvessels density (MVD) expressed by RECK is positively correlated with MVD expressed by CD34 and the glioma grade. The aim of this study was to characterize RECK expression in microvascular morphology pattern and investigate the role of RECK in glioblastomas.

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Alex John