ATL and HTLV-I: in vivo cell growth of ATL cells.
The mechanism of leukemogenesis or neoplastic cell growth in adult T cell leukemia (ATL) still remains unclear, although Tax of human T cell leukemia/lymphoma virus type I (HTLV-I), the etiologic virus, has been reported to affect the expression of various cellular genes which encode molecules involved in cell growth or cell death. We have studied the cell growth of HTLV-I-infected human T cells in severe combined immunodeficiency (SCID) mice and found that fresh leukemic cells or cell lines derived from leukemic cell clones but not HTLV-I-infected cell lines of nonleukemic cell origin showed tumorigenicity, and neither HTLV-I nor IL-2 expression was needed for cell growth in vivo, indicating that accumulating changes in addition to the initial events induced by HTLV-I infection were required for the development of ATL. The interaction between ATL cells and vascular endothelial cells appears to be one of the important factors which determine the pattern of organ infiltration by leukemic cells. E-selectin and its ligand are one of the major cell adhesion pathways between ATL cells and human umbilical vein endothelial cells (HUVEC). Another pathway that had not been identified was studied using newly developed monoclonal antibodies capable of blocking cell adhesion. The molecules which directly mediate adhesion between ATL cells and HUVEC were determined to be OX40 and gp34, a member of the tumor necrosis factor receptor (TNF-R) family and TNF family, respectively. The OX40/gp34 system may play a key role in the trafficking and homing of not only ATL cells but also activated normal T cells.
Uchiyama
T
T
Institute for Virus Research, Kyoto University, Japan.
D000818:Animals; D000954:Antigens, Surface; D002448:Cell Adhesion; D002455:Cell Division; D004730:Endothelium, Vascular / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D015458:Leukemia, T-Cell / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D008565:Membrane Proteins; D051379:Mice; D016513:Mice, SCID; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000954:Antigens, Surface; D008565:Membrane Proteins; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha