Cancer stem cell-like cells derived from malignant peripheral nerve sheath tumors

• Published in: PloS one Vol. 6; no. 6; p. e21099
• Main Authors: Spyra, Melanie, Kluwe, Lan, Hagel, Christian, Nguyen, Rosa, Panse, Jens, Kurtz, Andreas, Mautner, Victor Felix, Rabkin, Samuel David, Demestre, Maria
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-06-2011; Public Library of Science (PLoS)
• Subjects: Adherent cells; Animals; Biology; Biomarkers; Biomarkers, Tumor - genetics; Brain cancer; Cancer; CD90 antigen; Cell culture; Cell Differentiation; Cell growth; Cell Line, Tumor; Cell Proliferation; Cell Shape; Down-Regulation; Fibroblast growth factors; Flow cytometry; Gene expression; Growth factors; Humans; Immunodeficiency; Intermediate filament proteins; Kinases; Maxillofacial surgery; Medicine; Mice; Muscles; Mutation; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Nerve growth factor receptors; Nerve Sheath Neoplasms - pathology; Nestin; Neural cell adhesion molecule; Neuropathology; Oct-4 protein; Schwann cells; Smooth muscle; Spheres; Stem cell transplantation; Stem cells; Surgery; Tumors; Up-Regulation; United States > US; Massachusetts; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0021099

This study aims to examine whether or not cancer stem cells exist in malignant peripheral nerve sheath tumors (MPNST). Cells of established lines, primary cultures and freshly dissected tumors were cultured in serum free conditions supplemented with epidermal and fibroblast growth factors. From one established human MPNST cell line, S462, cells meeting the criteria for cancer stem cells were isolated. Clonal spheres were obtained, which could be passaged multiple times. Enrichment of stem cell-like cells in these spheres was also supported by increased expression of stem cell markers such as CD133, Oct4, Nestin and NGFR, and decreased expression of mature cell markers such as CD90 and NCAM. Furthermore, cells of these clonal S462 spheres differentiated into Schwann cells, smooth muscle/fibroblast and neurons-like cells under specific differentiation-inducing cultural conditions. Finally, subcutaneous injection of the spheres into immunodeficient nude mice led to tumor formation at a higher rate compared to the parental adherent cells (66% versus 10% at 2.5 × 10(5)). These results provide evidence for the existence of cancer stem cell-like cells in malignant peripheral nerve sheath tumors.