Integrin α3 is overexpressed in glioma stem-like cells and promotes invasion.

摘要: Gliomas are the most common primary tumours of central nervous system, with glioblastomas (GBMs) being malignant entity. The poor prognosis GBM patients is largely due to highly invasive nature these tumours. These invading cells extremely resistant radiation and chemotherapy, currently, there no anti-invasive therapies available (Nakada et al, 2007, 2013). A better understanding glioma invasion mechanism will help in developing therapeutic strategies combat GBM. An increasing body evidence suggests that a subpopulation tumour stem-like cell properties glioma, called either (GSCs) or glioma-initiating cells, responsible for formation, maintenance, progression (Singh 2003; Tamase 2009; Natsume 2011). rare characterised by their strong tumourigenic self-renewal ability. It critical understand how GSCs make them particularly difficult eradicate. From our data from other studies, it clear primarily (Liu 2006; Beier 2007; 2009). However, molecular features orchestrate process remain be elucidated. If we can identify molecules mediate GSC invasion, may represent promising targets development novel therapies. In GSCs, expression some neural stem markers such as nestin, SOX2, Musashi-1 has been reported (Ignatova 2002). In addition, CD133 evaluated an enrichment marker GSCs; however, several studies have demonstrated limitations specific (Beier Wang 2008). To date, perfect isolate alone. tend form neurospheres culture medium containing various kinds growth factors, epidermal factor (EGF) basic fibroblast (bFGF). neurosphere assay one reasonable methods isolating GSCs. previous report showed microenvironment induces differentiation, suggesting cannot maintain on its own (Pollard Therefore, obtain pure groups GSC. investigate characteristics using high numbers this study, used sorting order biology GSCs. Integrins surface migration-promoting receptor glycoproteins intracellular signals through interaction extracellular matrix (ECM). Integrins also significant role attachment ECM, formation adhesion complexes, consisting integrins many cytoplasmic proteins. particular, GBMs, participate regulation complex processes, growth, angiogenesis interacting ECM brain 2007). phase II clinical trial combining integrin inhibitor cilengitide standard chemoradiation improved survival newly diagnosed GBMs (Nabors 2012). Currently, under III trials results soon (Kurozumi 2012). In attach fibronectin laminin express α3. immunohistochemistry α3 localised especially surrounding vessels vivo. Additionally, overexpression increases migration whereas downregulation inhibits concomitant change phosphorylation level signal–regulated kinase (ERK) 1/2 pathway. suggest roles behavior activation ERK1/2.