Autocrine growth and progression of murine X-ray-induced T cell lymphomas.
Primary tumors of X-ray-induced murine T cell lymphomas comprise autocrine, growth factor-dependent cells. We have grown cell lines from primary X-ray-induced thymic lymphomas (PXTLs) under conditions which minimize the progression of the cells from factor dependence to factor independence. All (22) PXTL lines grown secrete a growth factor which supports their own growth and which we will call lymphoma growth factor LGF. LGF-dependent cells are non-tumorigenic or poorly tumorigenic, do not clone in soft agar, have no detectable rearrangements in the c-myc or Pim-1 region and possess near diploid or pseudodiploid karyotypes without evidence for trisomy of chromosomes nos. 15 or 17. PXTL-secreted LGF has no interleukin 1, 2, or 3 activity nor do LGF-secreting cells synthesize detectable IL-1, -2, or -3 mRNA. LGF contains no detectable interferon or GM-CSF activity in specific bioassays. Purified EGF, TGF beta, and interleukin preparations are inactive on LGF-dependent PXTL cells. Thus LGF appears to be a new growth factor that is required for the proliferation of non-progressed T lymphoma cells. Upon progression PXTL cells become growth factor independent, are highly tumorigenic in vivo, clone in soft agar, and assume a near triploid karyotype containing numerous chromosomal aberrations. Thus in X-ray-induced lymphomagenesis an autocrine, LGF-dependent phase precedes the progressed phase characterized by rearrangements in the myc and/or Pim-1 regions as well as by many chromosomal aberrations visible in the karyotype.
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D003470:Culture Media; D004261:DNA Replication; D006133:Growth Substances / Q000502:physiology; D008223:Lymphoma / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology*; D013936:Thymidine / Q000378:metabolism; D013953:Thymus Neoplasms / Q000473:pathology*; D014316:Tritium
D003470:Culture Media; D006133:Growth Substances; D014316:Tritium; D013936:Thymidine