Benign mesenchymal stromal cells in human sarcomas Journal Article

Authors: Morozov, A.; Downey, R. J.; Healey, J.; Moreira, A. L.; Lou, E.; Franceschino, A.; Dogan, Y.; Leung, R.; Edgar, M.; Laquaglia, M.; Maki, R. G.; Moore, M. A. S.
Article Title: Benign mesenchymal stromal cells in human sarcomas
Abstract: Purpose: Recent evidence suggests that at least some sarcomas arise through aberrant differentiation of mesenchymal stromal cells (MSCs), but MSCs have never been isolated directly from human sarcoma specimens. Experimental Design: We examined human sarcoma cell lines and primary adherent cultures derived from human sarcoma surgical samples for features of MSCs. We further characterized primary cultures as either benign or malignant by the presence of tumor-defining genetic lesions and tumor formation in immunocompromised mice. Results: We show that a dedifferentiated liposarcoma cell line DDLS8817 posesses fat, bone, and cartilage trilineage differentiation potential characteristic of MSCs. Primary sarcoma cultures have the morphology, surface immunophenotype, and differentiation potential characteristic of MSCs. Surprisingly, many of these cultures are benign, as they do not form tumors in mice and lack sarcoma-defining genetic lesions. Consistent with the recently proposed pericyte origin of MSCs in normal human tissues, sarcoma-derived benign MSCs (SDBMSCs) express markers of pericytes and cooperate with endothelial cells in tube formation assays. In human sarcoma specimens, a subset of CD146-positive microvascular pericytes expresses CD105, an MSC marker, whereas malignant cells largely do not. In an in vitro coculture model, SDBMSCs as well as normal human pericytes markedly stimulate the growth of sarcoma cell lines. Conclusions: SDBMSCs/pericytes represent a previously undescribed stromal cell type in sarcoma that may contribute to tumor formation. ©2010 AACR.
Keywords: immunohistochemistry; human tissue; protein expression; human cell; nonhuman; flow cytometry; protein localization; animal cell; mouse; animal tissue; cell function; cd34 antigen; cell structure; mesenchyme cell; animal experiment; animal model; cell differentiation; cancer cell culture; tumor xenograft; carcinogenesis; sarcoma; fluorescence in situ hybridization; bone; endoglin; immunophenotyping; matrigel; benign tumor; cell marker; hermes antigen; stroma cell; cd45 antigen; cd31 antigen; coculture; sarcoma cell; pericyte; cell strain; 5' nucleotidase; cd146 antigen; thy 1 antigen; cartilage; cell strain a 673; cell strain ddls 8817; cell strain u2os; mesenchymal stromal cell
Journal Title: Clinical Cancer Research
Volume: 16
Issue: 23
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2010-12-01
Start Page: 5630
End Page: 5640
Language: English
DOI: 10.1158/1078-0432.ccr-09-2886
PROVIDER: scopus
PUBMED: 21138865
PMCID: PMC3820159
Notes: --- - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Mark Allen Edgar
    45 Edgar
  2. Andre L Moreira
    170 Moreira
  3. Emil Lou
    11 Lou
  4. Roland C Leung
    3 Leung
  5. Robert Maki
    211 Maki
  6. Yildirim Dogan
    13 Dogan
  7. Robert J Downey
    202 Downey
  8. John H Healey
    374 Healey
  9. Malcolm A S Moore
    420 Moore