Functional cross talk between CXCR4 and PDGFR on glioblastoma cells is essential for migration

• Published in: PloS one Vol. 8; no. 9; p. e73426
• Main Authors: Sciaccaluga, Miriam, D'Alessandro, Giuseppina, Pagani, Francesca, Ferrara, Giuseppina, Lopez, Nadia, Warr, Tracy, Gorello, Paolo, Porzia, Alessandra, Mainiero, Fabrizio, Santoro, Antonio, Esposito, Vincenzo, Cantore, Giampaolo, Castigli, Emilia, Limatola, Cristina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.09.2013; Public Library of Science (PLoS)
• Subjects: Biology; Brain; Brain cancer; Brain tumors; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Chemokine receptors; Chemotaxis; Chemotaxis - drug effects; Conditioning; Crosstalk; CXCL12 protein; CXCR4 protein; Cytokines; Development and progression; Epidermal growth factor; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Glioblastoma; Glioblastoma - pathology; Glioblastoma cells; Glioblastomas; Glioma; Growth factor receptors; Growth factors; Health aspects; Humans; Infiltration; Kinases; Life Sciences; Metastases; Molecular modelling; Neurons and Cognition; Parenchyma; Phosphorylation; Physiological aspects; Platelet-derived growth factor; Receptor Cross-Talk; Receptor Cross-Talk - drug effects; Receptor, Platelet-Derived Growth Factor beta; Receptor, Platelet-Derived Growth Factor beta - genetics; Receptor, Platelet-Derived Growth Factor beta - metabolism; Receptors; Receptors, CXCR4; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; Signaling; Smooth muscle; Tyrosine; Tyrphostins; Tyrphostins - pharmacology; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073426

Glioblastoma (GBM) is the most common and aggressive form of brain tumor, characterized by high migratory behavior and infiltration in brain parenchyma which render classic therapeutic approach ineffective. The migratory behaviour of GBM cells could be conditioned by a number of tissue- and glioma-derived cytokines and growth factors. Although the pro-migratory action of CXCL12 on GBM cells in vitro and in vivo is recognized, the molecular mechanisms involved are not clearly identified. In fact the signaling pathways involved in the pro-migratory action of CXCL12 may differ in individual glioblastoma and integrate with those resulting from abnormal expression and activation of growth factor receptors. In this study we investigated whether some of the receptor tyrosine kinases commonly expressed in GBM cells could cooperate with CXCL12/CXCR4 in their migratory behavior. Our results show a functional cross-talk between CXCR4 and PDGFR which appears to be essential for GBM chemotaxis.