Overexpression of leptin receptor in human glioblastoma: Correlation with vasculogenic mimicry and poor prognosis

Abstract

Vasculogenic mimicry (VM) was an important tumor blood supply to complement the endothelial cell-dependent angiogenesis, while leptin and receptor (ObR) involved in angiogenesis in glioblastoma has been reported on previous study, but the relationship between ObR expression and VM formation in human glioblastoma tissues, as well as their prognostic significance still remains unclear. In our study, we found that VM recognized by CD31-/PAS+ immunohistochemical staining in glioblastoma tissues showed a positive correlation with leptin expression (r = 0.58, P < 0.01), as well as ObR expression in glioblastoma tissues (r = 0.61, P < 0.01). Association of glial to mesenchymal transition (GMT)-related molecular with ObR expression and VM formation in glioblastoma tissues indicated that ObR-positive glioblastoma cells with GMT phenotype might be more likely to constitute VM, and co-expression of ObR and CD133 or Nestin to constitute the channel impliated that ObR-positive glioblastoma cells displayed glioblastoma stem cells (GSC) properties. Moreover, Kaplan–Meier statistical analysis showed that patients with more VM or ObR expression displayed poorer prognosis for overall survival times than patients with less expression (VMhigh vs. VMlow: P = 0.033; ObRhigh vs. ObRlow: P = 0.009). And ObR+ glioblastoma cells with GSC characteristic were mostly involved in VM formation, whereas a little part of cells were also related to microvascular density (MVD), which suggested that ObR was an important target for anticancer therapy, so further related studies were needed to improve glioblastoma treatment.

The Expression of Leptin and Its Receptor During Tumorigenesis of Diffuse Gliomas such as Astrocytoma and Oligodendroglioma - Grade II, III and IV (NOS)

“…Significant expression of the leptin receptor has been shown in CD133+ cells and knockdown of leptin receptor effectively lowered the invasiveness of stem-like cells in gliomas and confirmed that JAK/STAT3 signaling is the molecular mechanism involved in the invasion of U87 glioma cells (Han et al, 2013). Another study suggests ObR as an important target for anti-cancer therapy as the ObR+ glioblastoma cells possessing glioblastoma stem cell properties were associated with vasculogenic mimicry formation and microvascular density (MVD) (Han et al, 2017). Extensive research has been carried out in mammary tumors with respect to these antibodies.…”

Leptin signaling axis specifically associates with clinical prognosis and is multifunctional in regulating cancer progression

“…Leptin receptor also displayed prognostic power in clinical. Patients of glioblastoma revealed poor prognosis as high leptin receptor levels were detected [ 15 ]. The association of leptin receptor with poor recurrence-free survival ( P =0.09) and cancer-specific survival ( P =0.01) by log-rank test was observed, and data from Cox regression analysis further characterized leptin receptor as an independent predictor of poor survival respectively with P =0.011 and 0.006 in upper tract urothelial carcinomas [ 16 ].…”

“…In 92% of the colorectal carcinoma cases with pronounced leptin receptor expression, high rate of angiogenesis case was observed alone with the correlation of low grade neoangiogenesis and leptin receptor absence (88.2% of the cases) [ 8 ]. In addition, the correlation of leptin receptor with vasculogenic mimicry (VM) formation had been reported in glioblastoma [ 15 ]. Moreover, HIF-1α RNA and protein expression of leptin and leptin receptor were high in tissue samples of oral squamous cell carcinoma which indicated the potential crosslink in regulating angiogenesis [ 40 ].…”

Caveolin-1 promotes tumor cell proliferation and vasculogenic mimicry formation in human glioma

“…VM is a non-endothelium-dependent vasculature to complement the endothelium-dependent vessels in providing oxygen and nutrients for malignant tumor cells. Although it has been widely investigated in the pathology of glioma which is characterized by increased microvasculature in tumor tissues [26,27], the molecular mechanism governing VM formation in glioma remains largely unknown. Our previous study has shown that Cav-1 and HIF-1α play important roles in the progress of glioma, and both of them are significantly associated with glioma prognosis [35].…”