Abstract
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 2.5×105). These results provide evidence for the existence of cancer stem cell-like cells in malignant peripheral nerve sheath tumors.
Highlights
Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas arising from peripheral nerves and have high rates of local recurrence and hematogenous metastasis [1]
Spheres formed at low density, as low as one cell per well, and propagated for at least 20 passages from the established MPNST cell line S462
We applied culture conditions optimised for neural stem cells, for the enrichment of cancer stem-like cells from MPNSTs
Summary
Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas arising from peripheral nerves and have high rates of local recurrence and hematogenous metastasis [1]. They account for 10% of all soft tissue sarcomas. Half of these malignancies occur in patients with neurofibromatosis type 1, a tumor suppressor gene syndrome with an incidence of approximately 1 in 3000. MPNST, especially those associated with neurofibromatosis type 1, are one of the most aggressive malignancies in humans with an extremely poor prognosis [2]
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