Human osteosarcomas inhibit hematopoietic colony formation: partial reversal by antibody to transforming growth factor-beta 1.
Recently we found that primary human osteoblast-like cells (HOBs) support hematopoietic progenitor cells (assayed by colony formation in methylcellulose) and long-term culture initiating (LTC-IC) activity in vitro. In the present investigation, we evaluate whether human osteosarcoma cells share in these activities. We observed that relative to controls, significantly fewer hematopoietic colonies were formed in the presence of HOS TE85, MG-63, SaOS-2, or U2-OS human osteosarcomas. In addition, neither MG-63 or SaOS-2 cells supported hematopoietic progenitor cell activity or LTC-IC activity in vitro. We established that the suppressive activity produced by the osteosarcomas is soluble, correlated with osteosarcoma cell number and is partially neutralized with antibody to TGF-beta 1,2,3. While it is clear that the osteosarcomas express several phenotypic characteristics of primary human osteoblasts, these data suggest that they may be functionally disregulated with regard to their ability to support normal hematopoiesis. For these reasons, caution should be exercised when evaluating osteoblastic and hematopoietic cell interactions based purely on the use of osteosarcoma cell lines.
Taichman
R S
RS
Department of Periodontics/Prevention/Geriatrics, University of Michigan School of Dentistry, Ann Arbor 48109-1078, USA. rtaich@umich.edu
Reilly
M J
MJ
Emerson
S G
SG
D000906:Antibodies / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000032:analysis; D001859:Bone Neoplasms / Q000473:pathology*; D002452:Cell Count; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017997:Leukotriene C4 / Q000276:immunology; D012516:Osteosarcoma / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000473:pathology
D000906:Antibodies; D018952:Antigens, CD34; D016212:Transforming Growth Factor beta; D017997:Leukotriene C4