Clinical Significance Of Vasculogenic Mimicry Research Articles

Mammalian target of rapamycin signaling is involved in the vasculogenic mimicry of glioma via hypoxia-inducible factor-1α.

The mammalian target of rapamycin(mTOR) is a crucial regulator in malignant gliomas. Vasculogenic mimicry(VM) describes functional channels established by highly malignant tumor cells that is different from endothelium-lined blood vessels. Our previous studies confirmed the existence and clinical significance of VM in medulloblastoma and glioblastoma. In the present study, by immunohistochemical and CD34/PAS histochemical double-staining, 34 cases (26.8%) with VM structures were identified among a total of 127 glioma cases, and these VM structures were associated with mTOR expression in the glioma specimens. Invitro, U87 malignant glioblastoma cells formed tube structures similar to HUVECs on Matrigel in 3D culture, and mTOR-specific inhibitor rapamycin inhibited VM formation in the U87 malignant glioblastoma cells under both normoxia and hypoxia. In addition, rapamycin and mTOR siRNA inhibited molecules in the signaling cascade of VM formation, particularly HIF-1α. Taken together, our results demonstrated that mTOR signaling is involved in VM formation, and may be a potential therapeutic target for gliomas.

Vasculogenic mimicry is a prognostic factor for postoperative survival in patients with glioblastoma

A previous report has confirmed the existence and clinical significance of vasculogenic mimicry (VM) in glioma. However, its conclusions about the negative clinical significance of VM in glioblastoma are based on a small group of patients and, thus, might be unconvincing. The aim of the present study was to reevaluate the clinical significance of VM in glioblastoma. Patients were classified as VM-positive or VM-negative according to CD34 and periodic acid-Schiff staining. The association between VM and the clinical characteristics of the patients was analyzed. Univariate and multivariate analyses were carried out to identify the independent prognostic factors for overall survival using the Cox regression hazard model. Survival times were estimated using the Kaplan-Meier method and compared using the log-rank test. Of all 86 glioblastomas, 23 were found to have VM. The presence of VM in glioblastoma was not associated with gender, age, Karnofsky performance status, hydrocephalus, tumor burden, microvessel density, tumor relapse, or the extent of tumor resection. The univariate and multivariate analyses revealed that VM is an independent prognostic factor for overall survival. The median survival time for patients with VM was 11.17 months compared with 16.10 months for those without VM (P = 0.017). In addition to VM, an age of 65 years or older, a KPS of 60 or less, a large tumor burden are significant prognostic factors for patient survival. Our data suggest that VM might be an independent adverse prognostic factor in newly diagnosed GBM, further prospective studies are needed to answer this question.

RETRACTED ARTICLE: Signaling pathways in tumor vasculogenic mimicry

Solid tumor growth is dependent on the development of an adequate blood supply. For years, sprouting angiogenesis has been considered as the exclusive mechanism of tumor vascularization. However, in recent years, another mechanism of tumor vascularization has been identified that does not involve endothelial cells, a process called vasculogenic mimicry (VM). VM describes the unique ability of highly aggressive tumor cells to form vessel-like networks by virtue of their high plasticity. VM has been observed in several tumor types, and its occurrence is strongly associated with poor prognosis. This review focuses on signaling molecules and cascades involved in VM. In addition, the clinical significance of VM regardless of anti-angiogenesis treatment modalities is described.

Clinical significance of vasculogenic mimicry in human gliomas

Vasculogenic mimicry (VM) is known as non-endothelial tumor cell-lined microvascular channels in aggressive tumors. We have previously found the presence of VM in high-grade gliomas. In this study, we aimed to identify VM patterns in gliomas and to explore their clinical significance. Tumor samples as well as their detailed clinical/prognostic data were collected from 101 patients. Vasculogenic mimicry in the glioma samples was determined by dual staining for endothelial marker CD34 and periodic acid–Schiff (PAS). Tumor samples were also immunohistochemically stained for Ki-67, VEGF, COX-2 and MMP-9. The association between VM and the clinical characteristics of the patients were analyzed. A Kaplan–Meier survival analysis and log-rank tests were performed to compare survival times of the patients. Vasculogenic mimicry was present in 13 out of 101 samples. The higher grade gliomas had a higher incidence of VM than that of lower grade gliomas (P = 0.006). Vasculogenic mimicry channels were associated with the expression of COX-2 and MMP-9 (P < 0.05). While there was no association between the existence of VM and the sex, age and preoperative epilepsy of the patients, or expression of Ki-67 and VEGF. However, patients with VM-positive gliomas survived a shorter period of time than those with VM negative gliomas (P = 0.027). Interestingly, in high-grade gliomas, the level of microvascular density was lower in VM positive tumors than those VM negative tumors (P = 0.039). Our results suggest that VM channels in gliomas correlate with increasing malignancy and higher aggressiveness, and may provide a complementation to the tumor’s blood supply, especially in less vascularized regions, which may aid in the identification of glioma patients with a poorer prognosis.

Formation mechanisms, regulating factors and clinical significance of vasculogenic mimicry

Vasculogenic mimicry (VM) can promote tumor growth, invasion, and metastasis. The formation of VM is regulated by various proteins including epithelial cell kinase, phosphoinositide-3 kinase, and hypoxia-inducible factor 1. Local microenvironment also plays an important role in regulating VM formation. Key words: Neovascularization,pathologic ; Neoplasms ; Hypoxia-inducible factor 1 ; Vasculogenic mimicry ;

Clinical significance of vasculogenic mimicry in human gliomas

Objective Vasculogenic mimicry (VM) is a newly recognized phenomena in many malignancies. However, we did not know its clinical significance in gliomas.This study was designed to investigate VM in gliomas and compare clinical data of patients. Methods One hundred and nine glioma specimens were collected for immunohistochemical staining of CD34 and PAS staining (dual staining) to verify the existence of VM.The clinical data of those glioma patients were collected and analyzed. Results The VMhad been considered for those stained positively for PAS, but negatively for endothelial marker-CD34.VM phenotypes were found in 13 specimens(11.9%). Most of the VM were found in higher grades gliomas:8 of 27 grade Ⅳ (29.6%), 3 of 41 grade Ⅲ(7.3%), and 2 of 36 grade Ⅱ(5.5%).While there was no VM found in grade Ⅰgliomas.The higher grade gliomas had higher incidence of VM expression than that of lower grade gliomas (P=0.028).There was no any association between the existence of VM and the sex,age and preoperative epilepsy of the patients.However,the patients whose tumors with VM expression survived shorter than those without VM (P=0.031).Conclusion VM exists in gliomas.Higher grades gliomas exhibit more VM than that of the lower grades gliomas. Glioma patients with VM may have poorer prognosis. Key words: Astrocytoma; Prognosis; Vasculogenic mimicry