The role of soluble growth factors in inducing transient growth and clonal extinction of stroma cell dependent erythroblastic leukemia cells.
A coculture system of a murine erythroblastic leukemia cell line (ELM-D) with its supportive stromal cell line (MS-5) was established. Long-term growth of ELM-D cells is strictly stroma cell dependent. Interaction between stem cell factor (SCF) and its receptor, c-kit, was demonstrated to be important for stroma cell-dependent growth by anti c-kit neutralizing monoclonal antibody (mAb) inhibition experiments. Significantly, soluble growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or SCF of MS-5 stromal cells (MS-5 CM) could replace the requirement of stroma cells for a considerable period. However, ELM-D cells maintained in these growth factors underwent clonal extinction after 3-6 weeks unless contact with stroma was re-established. Furthermore, IL-3 or GM-CSF acted in a dominant manner in inducing cell death in the presence of stroma cells. Cells showing clonal extinction undergo programmed cell death and do not differentiate. These altered growth properties of ELM-D cells exposed to soluble growth factors or to stroma cells appear to be analogous to those described for T or B cells primed by antigen presenting cells and then grown in growth factors.
Itoh
K
K
Heinrich-Pette Institute for Experimental Virology and Immunology, Hamburg University, Germany.
Friel
J
J
Laker
C
C
Zeller
W
W
Just
U
U
Bittner
S
S
Nibbs
R J
RJ
Harrison
P R
PR
Nishikawa
S I
SI
Mori
K J
KJ
Ostertag
W
W
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D003470:Culture Media; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012995:Solubility; D017154:Stromal Cells / Q000473:pathology
D003470:Culture Media; D006133:Growth Substances; D007377:Interleukin-3; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit