Endothelial vascular cell adhesion molecule 1 expression is suppressed by melanoma and carcinoma.
Vascular cell adhesion molecule 1 (VCAM-1) mediates extravasation of circulating leukocytes into inflamed tissues, and presumably, plays a role in the immigration of cytotoxic effector lymphocytes into tumor metastases. Since metastases are rarely cleared by blood-borne cells from the immune system, we asked whether the tumor may escape host defense by interfering with the mechanism of effector cell extravasation. Here we show that in mice and humans, VCAM-1 expression is repressed on tumor-infiltrating vascular endothelial cells in the lungs. On lung blood vessels distant from the tumor, VCAM-1 is constitutively expressed. When melanoma and endothelioma cells were cultured on either side of a Nucleopore membrane, the expression of VCAM-1 on the endothelioma cells was inhibited and VCAM-1 gene transcription was suppressed. We propose that the downregulation of VCAM-1 is a mechanism by which vascularized melanoma and carcinoma avoid invasion by cytotoxic cells of the immune system.
Piali
L
L
Basel Institute for Immunology, Switzerland.
Fichtel
A
A
Terpe
H J
HJ
Imhof
B A
BA
Gisler
R H
RH
D016475:3T3 Cells; D000328:Adult; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008969:Molecular Sequence Data; D012878:Skin Neoplasms / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D017931:DNA Primers; D019010:Vascular Cell Adhesion Molecule-1