Regulated expression of vascular cell adhesion molecule-1 in human malignant melanoma.
Expression of the endothelial adhesion molecule VCAM-1 was studied in human malignant melanoma lines by flow cytometry. Clones 2/4 and 2/14 (derived from the same lesion) had appreciable levels of VCAM-1 expression, whereas clone 2/21 and the lines A2058, Mel24, and A375 were negative. Clone 2/14 was selected for further analysis. Exposure to tumor necrosis factor (TNF) markedly augmented VCAM-1 on melanoma cells. Surface VCAM-1 was associated with expression of specific transcripts that were augmented by TNF. Analysis by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that TNF-stimulated melanoma cells expressed both 7 and 6 immunoglobulin domain transcripts with predominance of the longer species. Tumor necrosis factor--stimulated melanoma cells bound more VLA-4-expressing cells (melanoma and monocytes) than resting tumor cells and anti-VCAM-1 monoclonal antibodies significantly inhibited binding, thus suggesting that surface VCAM-1 on melanoma is functional. Analysis of melanoma tissue sections demonstrated that VCAM-1 is not a marker of transformation of melanocytes because it can be detected in benign nevi. Although, unlike ICAM-1, VCAM-1 is not correlated with tumor progression, its expression in a fraction of primary melanomas indicates that it may play a role in regulating host immune response and homotypic interactions in some malignant melanomas.
D001483:Base Sequence; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009000:Monocytes / Q000737:chemistry / Q000166:cytology; D010586:Phagocytes / Q000737:chemistry / Q000473:pathology; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D004273:DNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1