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Mucosal vascular addressin cell adhesion molecule‐1 is expressed outside the endothelial lineage on fibroblasts and melanoma cells
Author(s) -
Leung Euphemia,
Kanwar Rupinder K,
Kanwar Jagat R,
Krissansen Geoffrey W
Publication year - 2003
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.2003.t01-1-01175.x
Subject(s) - addressin , cell adhesion molecule , cell adhesion , microbiology and biotechnology , biology , tumor necrosis factor alpha , cell , immunology , biochemistry
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‐α (TNF‐α), and by freshly isolated and cultured primary mouse splenic and tail fibroblasts in the absence of TNF‐α stimulation. They were constitutively expressed by B16F10 melanoma cells, and expression was enhanced by cell activation with TNF‐α. 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‐α 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 α4β7‐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.