Mucosal vascular addressin cell adhesion molecule-1 is expressed outside the endothelial lineage on fibroblasts and melanoma cells.
Mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) is predominantly expressed on high endothelial venules in inflamed tissues where it assists with leucocyte extravasation. Here we report that MAdCAM-1 has the potential to be more widely expressed outside the endothelial cell lineage than previously appreciated. Thus, MAdCAM-1 RNA transcripts and cell-surface protein were expressed by NIH 3T3 fibroblasts following activation with tumour necrosis factor-alpha (TNF-alpha), and by freshly isolated and cultured primary mouse splenic and tail fibroblasts in the absence of TNF-alpha stimulation. They were constitutively expressed by B16F10 melanoma cells, and expression was enhanced by cell activation with TNF-alpha. Mucosal vascular addressin cell adhesion molecule-1 was expressed on the apical surface of isolated cells, but became predominantly localized to cell junctions in confluent cell monolayers, suggesting it may play a role in the homotypic aggregation of cells. Tumour necrosis factor-alpha enhanced the expression of a firefly luciferase reporter directed by the MAdCAM-1 promoter in NIH 3T3 and B16F10 cells. A DNA fragment extending from nt -1727 to -673 was sufficient to confer cell-type selective expression. Mucosal vascular addressin cell adhesion molecule-1 expressed by NIH 3T3 cells was biologically active, as it supported the adhesion of TK-1 T cells in an alpha4beta7-dependent fashion. The expression of MAdCAM-1 by fibroblasts, and melanomas suggests MAdCAM-1 may play a role in regulating host responses in the periphery, leucocyte transmigration across nonendothelial boundaries, or the homotypic interactions of some malignant melanomas.
Leung
Euphemia
E
Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Science, University of Auckland, Auckland, New Zealand.
Kanwar
Rupinder K
RK
Kanwar
Jagat R
JR
Krissansen
Geoffrey W
GW
D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D015815:Cell Adhesion Molecules; D018929:Cell Culture Techniques; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009088:Mucoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D012313:RNA / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C489082:Madcam1 protein, mouse; C504268:Madcam1 protein, rat; D009088:Mucoproteins; D014409:Tumor Necrosis Factor-alpha; D012313:RNA