Self-renewal of a transplantable murine leukemia induced by co-culture with human stromal cell lines.
The PGM-1 murine leukemic cell line can be serially transplanted in syngeneic C3H/HeJ mice but cannot be maintained in in vitro culture. In response to a wide range of known growth factors, the PGM-1 cells either die or differentiate into mature granulocytes and macrophages with loss of all clonogenic (i.e. agar culture colony-forming) cells within 7 days. In this report we show that coculture with human, but not mouse, bone marrow stromal cell lines allows maintenance of clonogenic cells. One line in particular (197/17) allowed continuous expansion of clonogenic cells with no evidence of differentiation. The maintenance of clonogenic cells correlated with maintenance of tumor stem cells. Even after 9 months continuous passaging on stromal cells, the cultured cells produced tumors on injection into syngeneic mice with the same latency as cells from explanted tumors. We demonstrated that this activity was due to a soluble factor in 197/17 conditioned medium. An extensive survey of known factors, either alone or in combination, failed to reproduce this effect, implying that the effect was due to a novel factor acting on self-renewal of early stem cells.
Duhrsen
U
U
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Australia.
Novotny
J
J
Boyd
A W
AW
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D002461:Cell Line, Transformed; D017077:Culture Media, Conditioned; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007953:Leukemia, Radiation-Induced / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology; D013045:Species Specificity; D017154:Stromal Cells / Q000166:cytology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000954:Antigens, Surface; D017077:Culture Media, Conditioned; D006133:Growth Substances