@article{c7d0f208f3e440e49eafe27062a4a856,
title = "Induction of Abnormal Proliferation by Nonmyelinating Schwann Cells Triggers Neurofibroma Formation",
abstract = "Recent evidence suggests that alterations in the self-renewal program of stem/progenitor cells can cause tumorigenesis. By utilizing genetically engineered mouse models of neurofibromatosis type 1 (NF1), we demonstrated that plexiform neurofibroma, the only benign peripheral nerve sheath tumor with potential for malignant transformation, results from Nf1 deficiency in fetal stem/progenitor cells of peripheral nerves. Surprisingly, this did not cause hyperproliferation or tumorigenesis in early postnatal period. Instead, peripheral nerve development appeared largely normal in the absence of Nf1 except for abnormal Remak bundles, the nonmyelinated axon-Schwann cell unit, identified in postnatal mutant nerves. Subsequent degeneration of abnormal Remak bundles was accompanied by initial expansion of nonmyelinating Schwann cells. We suggest abnormally differentiated Remak bundles as a cell of origin for plexiform neurofibroma.",
keywords = "CELLCYCLE, STEMCELL",
author = "Huarui Zheng and Lou Chang and Neha Patel and Jiong Yang and Lori Lowe and Burns, {Dennis K.} and Yuan Zhu",
note = "Funding Information: We thank M. Hancock, J. Tomasek, L. Liu, and A. Wang for technical assistance; members of the Zhu lab for support; Dr. N. Joseph for assistance on FACS analysis; Drs. L. Parada and M. Giovannini for providing critical mouse strains and generous support in the early phases of the project; Dr. P. Charnay for Krox20 -cre mice; S. Meshinchi at the MIL core facility for EM analysis; J. Kazemi at CSCAR for statistical analysis; Dr. N. Heintz for BLBP antibody and Drs. Y. Shen and K. Meiri for GAP-43 antibody; and Drs. E. Fearon, S. Morrison, and S. Weiss for critically reading the manuscript. This work is supported by grants from the American Cancer Society (ACS, no. RSG DDC-110857), the Department of Defense (DOD, NF050041), the Comprehensive Cancer Center and Biological Sciences Scholars Program of the University of Michigan (Y.Z.). Y.Z. is an ACS, GMCR, and BSSP Scholar. ",
year = "2008",
month = feb,
day = "5",
doi = "10.1016/j.ccr.2008.01.002",
language = "English (US)",
volume = "13",
pages = "117--128",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}