New Insight on the Role of Transient Receptor Potential (TRP) Channels in Driven Gliomagenesis Pathways

Abstract

Gliomas are primary brain tumours believed to arise from glial cells or their progenitors. They account for 78% of malignant brain tumours (Shwartzbaum et al., 2006). The vast majority of gliomas is high-grade glioblastoma multiforme (GBM), and is characterized by almost unrestrained growth. Consequently, the median survival of patients with GBM was approximately 12 months (Huncharek & Muscat, 1998). While research has generated abundant information regarding the growth characteristics of these cancers, clinical care remains palliative and the prognosis dismal (Butowski et al., 2006). Gliomagenesis and progression are complex processes only partly understood. At molecular level, tumor progression and the associated heterogeneity is likely the result of multiple mutations in certain key signaling proteins (Furnari et al., 2007). Among these proteins, the Transient Receptor Potential (TRP) channel family has been identified to profoundly affect a variety of physiological and pathological processes (Kiselyov et al., 2007; Nilius et al., 2007). Members of TRP channels control cellular homeostasis by regulating calcium flux, cell proliferation, differentiation and apoptosis; moreover, in the last years an additional role for TRP ion channel family in malignant cancer growth and progression has been recognized (Xu et al., 2001; Wisnoskey et al., 2003; Xin et al., 2005; Bidaux et al., 2007; Prevarskaya et al., 2007; Gkika & Prevarskaya, 2009). Approximately thirty TRPs have been identified to date, and are classified in seven different families: TRPC (Canonical), TRPV (Vanilloid), TRPM (Melastatin), TRPML (Mucolipin), TRPP (Polycystin), and TRPA (Ankyrin transmembrane protein) and TRPN (NomPC-like) (Montell, 2003) (Fig.1). The expression levels and activity of members of the TRPC, TRPM, and TRPV families have been correlated with malignant growth and progression (Duncan et al., 1998; Tsavaler et al., 2001; Wissenbach et al., 2001; Thebault et al., 2006; Amantini et al., 2007; Caprodossi et al., 2008; Nabissi et al., 2010). TRP channels may regulate glioma growth and progression at different levels by controlling cell proliferation, inhibiting apoptosis, stimulating angiogenesis and triggering the migration and the invasion during tumor progression (Table 1).