Heterogeneity in human melanoma cell adhesion to cytokine activated endothelial cells correlates with VLA-4 expression.
Tumor cell attachment to endothelial cells (EC) is one of the critical steps of the metastatic process. It was previously reported that interleukin 1 treatment of EC induces expression of membrane molecules that promote tumor cell adhesion. In this paper we report that a panel of six clones isolated from a human metastatic melanoma presented a marked heterogeneity in their ability to adhere to interleukin 1 activated EC. This was correlated with integrin VLA-4 expression by the clones. Antibodies directed to VLA-4 and to its endothelial ligand INCAM110/VCAM-1 abolished interleukin 1 induced increase in melanoma cell adhesion to EC. These data demonstrate intratumor heterogeneity in the expression of VLA-4 and that this can represent a crucial determinant of tumor cell interaction with EC during secondary spread.
Martìn-Padura
I
I
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Mortarini
R
R
Lauri
D
D
Bernasconi
S
S
Sanchez-Madrid
F
F
Parmiani
G
G
Mantovani
A
A
Anichini
A
A
Dejana
E
E
D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008545:Melanoma / Q000378:metabolism* / Q000503:physiopathology; D016029:Receptors, Very Late Antigen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D016029:Receptors, Very Late Antigen; D011994:Recombinant Proteins