title: Reconstitution of Schwannian stroma in neuroblastomas using human bone marrow stromal cells.
abstract: The Schwannian stroma in neuroblastomas is related to patient prognosis. There is debate surrounding the origin of Schwannian stroma in neuroblastomas: one theory is that the Schwann cells are derived from neoplastic cells, and the other is that they arise from normal cells surrounding the neuroblastoma. We examined whether human bone marrow stromal cells (hBMSCs) or human mesenchymal stem cells (hMSCs) could differentiate into Schwann cells in neuroblastomas. hBMSCs or hMSCs along with enhanced green fluorescent protein (EGFP) were injected into xenotransplanted neuroblastomas in nonobese diabetic mice with severe combined immunodeficiency and the resulting tumors were analyzed using immunohistochemistry. HBMSCs and hMSCs were co-cultured with neuroblastoma cells, and the induction of Schwann cell-specific molecules, S100beta and Egr-2, was monitored. S100beta-positive Schwannian stroma was observed only in neuroblastomas containing either hBMSCs or hMSCs, but not in neuroblastomas lacking these cells. Double staining with anti-S100 and anti-EGFP antibodies showed that S100-positive cells in neuroblastomas were also EGFP-positive. By contrast, hBMSCs did not develop into Schwann cells in Ewing's sarcoma, demonstrating that differentiation of transplanted hBMSCs or hMSCs into Schwann cells occurs specifically in neuroblastomas. Both S100beta and Egr-2 were expressed in hBMSCs or hMSCs co-cultured with neuroblastoma cells. HBMSCs or hMSCs may contribute to the formation of human tumor stroma. The Schwannian stroma of neuroblastomas appears to be derived from nonneoplastic stromal cells rather than neuroblastoma cells, further clarifying its developmental origins.
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Du
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Hozumi
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hata
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology*; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D009368:Neoplasm Transplantation; D009414:Nerve Growth Factors / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology*
chemical_list: D051767:Early Growth Response Protein 2; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
references.citation: Am J Pathol. 2005 Mar;166(3):891-900
references.pmid: 15743800
references.citation: Microsurgery. 1998;18(7):397-405
references.pmid: 9880154
references.citation: Clin Neuropathol. 1994 Jul-Aug;13(4):171-80
references.pmid: 7955661
references.citation: Acta Neuropathol. 1989;79(2):217-21
references.pmid: 2480694
references.citation: Cancer. 1999 Jul 15;86(2):349-63
references.pmid: 10421272
references.citation: Nature. 1999 Oct 14;401(6754):670-7
references.pmid: 10537105
references.citation: J Cutan Pathol. 2002 Aug;29(7):397-406
references.pmid: 12139634
references.citation: Mol Cancer Ther. 2006 Mar;5(3):755-66
references.pmid: 16546991
references.citation: Dev Biol. 2002 Jun 15;246(2):245-58
references.pmid: 12051814
references.citation: Br J Haematol. 2007 Jun;137(6):491-502
references.pmid: 17539772
references.citation: Eur J Cancer. 1995;31A(4):429-34
references.pmid: 7576940
references.citation: J Neurosci Res. 1997 Dec 1;50(5):702-12
references.pmid: 9418958
references.citation: Science. 2000 Aug 18;289(5482):1197-202
references.pmid: 10947988
references.citation: Clin Cancer Res. 2005 Nov 1;11(21):7749-56
references.pmid: 16278396
references.citation: Cell Growth Differ. 1991 Oct;2(10):487-93
references.pmid: 1751405
references.citation: Nature. 2001 May 17;411(6835):375-9
references.pmid: 11357145
references.citation: J Exp Med. 2006 May 15;203(5):1235-47
references.pmid: 16636132
references.citation: Gene Ther. 2004 Jul;11(14):1155-64
references.pmid: 15141157
references.citation: Cancer Res. 2004 Dec 1;64(23):8492-5
references.pmid: 15574751
references.citation: Brain Res. 1987 Nov 24;426(2):349-57
references.pmid: 2446713
references.citation: Cancer Res. 2005 Apr 15;65(8):3193-9
references.pmid: 15833850
references.citation: Prog Brain Res. 2001;132:3-11
references.pmid: 11544997
references.citation: Oncogene. 2001 Apr 12;20(16):1981-9
references.pmid: 11360182
references.citation: N Engl J Med. 1996 Jun 6;334(23):1505-11
references.pmid: 8618605
references.citation: Cancer. 2002 Mar 1;94(5):1574-83
references.pmid: 11920516
references.citation: Med Pediatr Oncol. 2001 Jan;36(1):163-8
references.pmid: 11464875
references.citation: Int J Dev Biol. 2002;46(4):559-67
references.pmid: 12141444
references.citation: Oral Oncol. 2004 Nov;40(10):1048-56
references.pmid: 15509497
references.citation: Cancer Res. 2001 Sep 15;61(18):6892-8
references.pmid: 11559566
references.citation: Eur J Biochem. 2000 Dec;267(24):6972-5
references.pmid: 11106405
references.citation: Cancer Res. 2005 Apr 15;65(8):3307-18
references.pmid: 15833864
references.citation: Cancer Res. 2002 Jul 1;62(13):3603-8
references.pmid: 12097260
references.citation: Nat Med. 2001 Nov;7(11):1194-201
references.pmid: 11689883
references.citation: Science. 2004 Feb 6;303(5659):848-51
references.pmid: 14764882
references.citation: Glia. 2002 Mar 1;37(3):206-18
references.pmid: 11857679
references.citation: Br J Cancer. 2002 Apr 8;86(7):1110-6
references.pmid: 11953858
references.citation: Glia. 2001 Aug;35(2):81-9
references.pmid: 11460264
references.citation: Science. 1999 Apr 2;284(5411):143-7
references.pmid: 10102814
references.citation: J Invest Dermatol. 2005 Mar;124(3):638-43
references.pmid: 15737206
references.citation: Exp Cell Res. 2005 Jun 10;306(2):330-5
references.pmid: 15925588
references.citation: Cancer. 1999 Jul 15;86(2):364-72
references.pmid: 10421273
references.citation: Clin Exp Metastasis. 1999 Jun;17(4):333-40
references.pmid: 10545020