Modulation of L-selectin ligand expression during an immune response accompanying tumorigenesis in transgenic mice.
Immune surveillance depends on lymphocyte access to tissue. Lymphocytes emigrate from blood when adhesion receptors such as L-selectin and the alpha 4 beta 7 integrin on these cells bind to ligands expressed on venular endothelium. Among transgenic mouse lines expressing an oncoprotein (Tag) in islet beta cells, some recognize Tag as nonself. In these mice, Tag expression elicits both beta cell hyperplasia with subsequent progression to tumors and lymphocytic infiltration. Endothelial ligands for L-selectin and alpha 4 beta 7 were upregulated in infiltrated islets in these transgenic mice. These ligands were not expressed in tumors, which were devoid of lymphocytic infiltration. In contrast, the adhesion molecules PECAM-1, ICAM-1, and VCAM-1 were expressed on endothelium in both noninfiltrated tumors and infiltrated islets. Thus, upregulation of expression of endothelial ligands for L-selectin and alpha 4 beta 7 may contribute to autoimmune infiltration. Repression of expression of these same ligands may be involved in the failure of tumor immunity.
Onrust
S V
SV
Department of Anatomy, University of California, San Francisco 94143, USA.
Hartl
P M
PM
Rosen
S D
SD
Hanahan
D
D
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis*; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006965:Hyperplasia; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000032:analysis; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D019041:L-Selectin / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D009077:Mucins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D009088:Mucoproteins / Q000032:analysis; D009389:Neovascularization, Pathologic; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis
D000954:Antigens, Surface; D000957:Antigens, Viral, Tumor; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C069886:L-selectin counter-receptors; D008024:Ligands; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009077:Mucins; D009088:Mucoproteins; D012333:RNA, Messenger; D019041:L-Selectin; C075185:sulfated glycoprotein p50