In vitro growth patterns and autocrine production of hemopoietic colony stimulating factors: analysis of leukemic populations arising in irradiated mice from cells of an injected factor-dependent continuous cell line.
Cells of the factor-dependent hemopoietic cell line FDC-P1 become leukemic when injected intravenously to irradiated syngeneic mice. An analysis of 117 cell lines derived from 17 such leukemic mice showed that they displayed different patterns of growth in vitro ranging from full autonomy to absolute dependency on stimulation by granulocyte-macrophage colony stimulating factor (GM-CSF) or multipotential colony stimulating factor (multi-CSF). In contrast to parental FDC-P1 cells, even the factor-dependent variant cell lines were tumorigenic in vivo. The behavior of these latter cell lines could not be explained by hyperresponsiveness to CSFs or prolonged survival in the absence of CSFs. Conditioned media and cell lysates from leukemic cell lines from 8 animals contained variable levels of GM-CSF or multi-CSF. Proliferation of a GM-CSF-producing cell line was inhibited by anti-GM-CSF antibody, while both the parental FDC-P1 line and a leukemic line secreting multi-CSF remained unaffected. The patterns of growth in vitro of the leukemic cells tended to correlate with the amounts of CSFs produced. The observations show that leukemic transformation of FDC-P1 cells in vivo is frequently linked to autogenous production of hemopoietic growth factors. The range of abnormal in vitro growth patterns observed includes those typical of human acute myeloid leukemia, and the in vivo transformation model may be useful in analyzing the mechanisms leading to the development of this human disease.
Dührsen
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Cancer Research Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
D000818:Animals; D000906:Antibodies; D002455:Cell Division; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000494:pharmacology; D003470:Culture Media; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007621:Karyotyping; D007942:Leukemia, Experimental / Q000235:genetics / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA
D000906:Antibodies; D003115:Colony-Stimulating Factors; D003470:Culture Media; D006133:Growth Substances; D016178:Granulocyte-Macrophage Colony-Stimulating Factor