A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma

• Published in: Cancer cell Vol. 17; no. 4; pp. 362 - 375
• Main Authors: Chen, Ruihuan, Nishimura, Merry C., Bumbaca, Stephanie M., Kharbanda, Samir, Forrest, William F., Kasman, Ian M., Greve, Joan M., Soriano, Robert H., Gilmour, Laurie L., Rivers, Celina Sanchez, Modrusan, Zora, Nacu, Serban, Guerrero, Steve, Edgar, Kyle A., Wallin, Jeffrey J., Lamszus, Katrin, Westphal, Manfred, Heim, Susanne, James, C. David, VandenBerg, Scott R., Costello, Joseph F., Moorefield, Scott, Cowdrey, Cynthia J., Prados, Michael, Phillips, Heidi S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.04.2010
• Subjects: AC133 Antigen; Antigens, CD - analysis; Antigens, CD - genetics; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Cell Differentiation; Cell Division; CELLCYCLE; Cellular Structures - pathology; Flow Cytometry; Gene Expression Profiling; Genetic Linkage; Glioblastoma - genetics; Glioblastoma - pathology; Glycoproteins - analysis; Glycoproteins - deficiency; Glycoproteins - genetics; Humans; Immunohistochemistry; Kinetics; Neoplastic Stem Cells - pathology; Neoplastic Stem Cells - transplantation; Peptides - analysis; Peptides - deficiency; Peptides - genetics; CELLCYCLE
• ISSN: 1535-6108; 1878-3686; 1878-3686
• DOI: 10.1016/j.ccr.2009.12.049

The neural stem cell marker CD133 is reported to identify cells within glioblastoma (GBM) that can initiate neurosphere growth and tumor formation; however, instances of CD133 − cells exhibiting similar properties have also been reported. Here, we show that some PTEN-deficient GBM tumors produce a series of CD133 + and CD133 − self-renewing tumor-initiating cell types and provide evidence that these cell types constitute a lineage hierarchy. Our results show that the capacities for self-renewal and tumor initiation in GBM need not be restricted to a uniform population of stemlike cells, but can be shared by a lineage of self-renewing cell types expressing a range of markers of forebrain lineage. ► GBM PTEN deficiency correlates with successfully expandable neurosphere culture ► Identification of self-renewing CD133 − cell type generating CD133 + and CD133 − progeny ► Evidence for lineage hierarchy of self-renewing, tumor-initiating cells in GBM ► GBM cell lineage with graded spectrum of cancer stem cell competencies