Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain

Abstract

Stem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we demonstrate that SCF directly activates brain microvascular endothelial cells (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human gliomas express SCF in a grade-dependent manner and induce normal neurons to express SCF in brain regions infiltrated by glioma cells, areas that colocalize with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated angiogenesis and glioma growth in vivo, whereas overexpression of SCF is associated with shorter survival in patients with malignant gliomas. Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain.

The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK

“…C Andradas et al (Freije et al, 2004;Sun et al, 2006). We observed, as for breast tumors, a link between high GPR55 levels and the more advanced stages of pancreatic ductal adenocarcinoma progression (Figure 1c) as well as higher histological grades (III and IV) in glioblastomas ( Figure 1d).…”

MMSET is overexpressed in cancers: Link with tumor aggressiveness

“…Thus, we looked for whether MMSET expression could be associated with tumor progression and prognosis. MMSET was significantly overexpressed in oligodendroglioma grade III compared to grade II (P = .009) [11] ( Figure 1) in agreement with previous data [9]; in patients presenting advanced bladder carcinoma (grade II and III) compared to grade I in four independent studies (P = 4E-6, P = .0001, P = .004, P = .008) [19; 43; 44; 45]; in breast carcinoma grades II and III compared to grade I in four independent studies (P = 2.2E-6, P = 9.1E-4, P = .014, P = .017) [46; 47; 48; 49]; in advanced prostate carcinoma grades VII, VIII and IX compared to grade VI (P = 1.4E-4 [50]; in no differentiated hepatocellular carcinoma compared to differentiated hepatocellular carcinoma (P = 7.2E-5) [15]; in undifferentiated compared to differentiated head and neck cancer (P = .002) [17]; in undifferentiated compared to differentiated cervical carcinoma [51]; in advanced papillary renal cell carcinoma stages III and IV compared to stages I and II (P = .0039) [52] (Figure 1). Furthermore, as it has been demonstrated in MM, MMSET expression is associated with bad prognostic in others cancers (Figure 2).…”

Post-translational regulation of PTEN

“…This can occur as a consequence of direct mutation of PTEN gene itself and/or alteration of its degradation machinery, such as overexpression or superactivation of NEDD4-1. Indeed, it has been reported that NEDD4-1 expression level is very high in many human cancer cell lines (Anan et al, 1998), and it has also been documented to be highly overexpressed in a large cohort of human glioma samples (Oncomine database; Sun et al, 2006). Although the relationship of NEDD4-1 overexpression with PTEN in these gliomas is not clear, the important role of PTEN in gliomas warrants further investigation.…”