Contributions of autocrine and non-autocrine mechanisms to tumorigenicity in a murine model for leukaemia.
We have surveyed the possible mechanisms by which factor-dependent FDC-P1 cells can be rendered leukaemogenic by exposure of cells to the chemical mutagen, ethyl methane sulphonate. Cell lines established on the basis of an ability to proliferate in the absence of exogenous colony-stimulating factors (CSFs) fall into two classes; those that are maximally stimulated and show no evidence of production of CSFs and others that grow in a density-dependent manner and express granulocyte-macrophage CSF (GM-CSF). That the growth of this latter class can be suppressed by the inclusion of antisense GM-CSF oligonucleotides in the growth medium indicates that the basis for their in vitro proliferation, and probably their ability to initiate the formation of transplantable leukaemias, is autocrine stimulation by GM-CSF. The ability of low levels of CSF to sustain autocrine stimulation, as we have shown, raises the possibility of an autocrine basis for the proliferation of certain human leukaemic cells. The ability to detect low concentrations of CSFs and develop in vitro assays that closely mimic the conditions that exist in vivo will be important aids in the classification of human leukaemias.
Dunn
A R
AR
Ludwig Institute for Cancer Research, Melbourne Tumor Biology Branch, Royal Melbourne Hospital, Victoria, Australia.
Wilks
A F
AF
D000818:Animals; D002461:Cell Line, Transformed; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D007942:Leukemia, Experimental / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D009153:Mutagens / Q000378:metabolism
D003115:Colony-Stimulating Factors; D009153:Mutagens