Induction of thymus-reestablishing lymphoid tumors by a murine leukemia virus carrying the avian v-myc oncogene.
Primary lymphoid tumor cells induced by wild type or recombinant Moloney murine leukemia viruses were inoculated intravenously into sublethally irradiated, syngeneic mice and compared for their ability to reestablish in the recipient thymus and spleen. Lymphoid tumors induced by one recombinant, M-MuLV(myc), containing the v-myc oncogene from the avian MC29 retrovirus consistently reestablished in the thymus and spleen of recipient mice. Since tumors in the recipient thymus and spleen could have arisen by infection of host cells, or could reflect an expansion of a minor subpopulation from the donor tumor, we verified the donor and clonal origin of these tumors by Southern blot analysis using a virus-specific probe. As few as 500 of these tumor cells could migrate to the thymus via the blood and flourish in that microenvironment. In contrast, the majority of tumors induced by wild type M-MuLV or two other M-MuLV recombinants not containing v-myc sequences, inefficiently reestablished in the thymus of recipient mice following i.v. inoculation, although splenic tumors developed. These tumors could, however, multiply within the recipient thymus when inoculated intrathymically. Thus, the inability of tumors induced by wild type M-MuLV or M-MuLV recombinants lacking v-myc to reestablish in the thymus following i.v. inoculation appears to reflect inefficient 'thymic homing' rather than the ability to grow in the thymic microenvironment. Collectively, our data suggest that the thymic homing ability of M-MuLV(myc)-induced tumor cells is related to the presence of v-myc sequences or to the cell type transformed by M-MuLV(myc). Thus, we suggest that these cells may provide a useful model for studying how blood-borne metastatic cells, and possibly normal lymphocytes, enter the thymus by way of the microvasculature.
Spencer
R H
RH
Department of Microbiology, University of California, Irvine 92717.
Brightman
B K
BK
Trepp
D J
DJ
Fan
H
H
Chandy
K G
KG
D000818:Animals; D002455:Cell Division; D016259:Genes, myc; D009052:Leukemia Virus, Murine / Q000235:genetics*; D007942:Leukemia, Experimental / Q000209:etiology*; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D013953:Thymus Neoplasms / Q000209:etiology*