RT Journal Article
SR Electronic
T1 Expression of the Receptor Tyrosine Kinase Tie2 in Neoplastic Glial Cells Is Associated with Integrin β1-Dependent Adhesion to the Extracellular Matrix
JF Molecular Cancer Research
JO Mol Cancer Res
FD American Association for Cancer Research
SP 915
OP 926
DO 10.1158/1541-7786.MCR-06-0184
VO 4
IS 12
A1 Lee, Ok-Hee
A1 Xu, Jing
A1 Fueyo, Juan
A1 Fuller, Gregory N.
A1 Aldape, Kenneth D.
A1 Alonso, Marta M.
A1 Piao, Yuji
A1 Liu, Ta-Jen
A1 Lang, Frederick F.
A1 Bekele, B. Nebiyou
A1 Gomez-Manzano, Candelaria
YR 2006
UL http://mcr.aacrjournals.org/content/4/12/915.abstract
AB The abnormal function of tyrosine kinase receptors is a hallmark of malignant gliomas. Tie2 receptor tyrosine kinase is a specific endothelial cell receptor whose function is positively regulated by angiopoietin 1 (Ang1). Recently, Tie2 has also been found in the nonvascular compartment of several tumors, including leukemia as well as breast, gastric, and thyroid cancers. There is, however, little information on the function of the Ang1/Tie2 pathway in the non–stromal cells within human tumors. We found that surgical glioblastoma specimens contained a subpopulation of Tie2+/CD31− and Tie2+/GFAP+ cells, suggesting that Tie2 is indeed expressed outside the vascular compartment of gliomas. Furthermore, analysis of a tissue array consisting of 116 human glioma samples showed that Tie2 expression in the neoplastic glial cells was significantly associated with progression from a lower to higher grade. Importantly, Ang1 stimulation of Tie2+ glioma cells resulted in increased adherence of the cells to collagen I and IV, suggesting that Tie2 regulates glioma cell adhesion to the extracellular matrix. Conversely, the down-regulation of Tie2 levels by small interference RNA or the addition of soluble Tie2 abrogated the Ang1-mediated effect on cell adhesion. In studying the expression of cell adhesion molecules, we found that Tie2 activation was related to the up-regulation of integrin β1 levels and the formation of focal adhesions. These results, together with the reported fact that malignant gliomas express high levels of Ang1, suggest the existence of an autocrine loop in malignant gliomas and that a Tie2-dependent pathway modulates cell–to–extracellular matrix adhesion, providing new insights into the highly infiltrative phenotype of human gliomas. (Mol Cancer Res 2006;4(12):915–26)