Decreased expression of ICAM-1 and its induction by tumor necrosis factor on breast-cancer cells in vitro.
In order to study adhesion-molecule expression and its consequences for cellular recognition, the presence of adhesion molecules ICAM-1, VCAM-1, VLA-4, LFA-1, alpha, LFA-1 beta, LFA-3, beta1-integrin and beta3-integrin was studied on specimens from breast tissue by immunohistochemistry and on cells from breast cell lines propagated in vitro. Breast-cancer tissue and the breast-cancer cell lines MCF-7, SK-BR-3 and ZR-75-1 showed expression of ICAM-1 and VLA-4 significantly lower than that of benign breast cells or normal breast epithelium. Of various cytokines tested, including recombinant human (rh) interleukin-6 (IL-6), rh tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), granulocyte/macrophage-colony-stimulating-factor (GM-CSF), interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma), only TNF was able to re-induce expression of ICAM-1 on cells from MCF-7, SK-BR-3 and ZR-75-1. Further, the ability of either unstimulated or lymphokine-stimulated killer (LAK) cells to recognize and lyse native or TNF-stimulated breast-cancer cells was studied. Whereas neither unstimulated lymphocytes or LAK cells were able to lyse untreated breast-cancer cells deficient for ICAM-1 expression, pre-treatment of tumor cells with TNF led to increased tumor-cell lysis. Anti-ICAM-1 antibodies, and pre-treatment of tumor cells with anti-TNF-receptor antibodies, abrogated these findings, corroborating their specificity. We thus conclude that the defective expression of ICAM-1 in our model might constitute a mechanism by which breast-cancer cells escape immunologic recognition and lysis by appropriate effector cells.
Budinsky
A C
AC
Department of Internal Medicine I, University Hospital, Vienna, Austria.
Brodowicz
T
T
Wiltschke
C
C
Czerwenka
K
K
Michl
I
I
Krainer
M
M
Zielinski
C C
CC
D000906:Antibodies / Q000276:immunology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000906:Antibodies; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1