Decreased expression of ICAM-1 and its induction by tumor necrosis factor on breast-cancer cellsin vitro

Abstract

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, b1-integrin and b3-integrin was studied on specimens from breast tissue by immunohistochemistry and on cells from breast cell lines propagated in vitro. Breastcancer 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-a), interleukin 2 (IL-2), granulocyte/macrophagecolony-stimulating-factor (GM-CSF), interferon-alpha (IFN-a) and interferon-gamma (IFN-g), only TNF was able to reinduce 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 ( Cellular adhesion has been shown to be mediated by membraneassociated adhesion molecules (Butcher, 1991) and is physiologically important for a series of mechanisms, including morphogenesis (Krotoski et al., 1986), cell migration (Albelda, 1993) and cellular interaction (Hynes, 1992). These are essential for the proper function of immunologic processes (Mackay and Imhof, 1993) and the development of tumor metastases (Behrens, 1993). In the last instance, variation in adhesion-molecule expression influences not only the metastatic cascade, including the destruction of normal cell-cell and cell-substrate cohesion, the penetration of tumor cells into the vascular system and the further spread into distant organs (Frenette and Wagner, 1996), but also the recognition of tumor cells by lytic effector cells (Kushner and Cheung, 1992). Thus, defective regulation of adhesion-molecule expression by tumor cells might play an important role in the evolution of tumors, their metastatic spread and their escape from immunologic surveillance.In the present study, therefore, we investigated the expression of various adhesion molecules, first, on pathohistologic specimens from benign and malignant breast tissue by immunohistochemistry and, later, on various benign and malignant breast cell lines propagated in vitro. Moreover, like Hutchins and Steel (1994), we studied the ability of various cytokines to modulate adhesionmolecule expression on cells derived from breast-cancer lines and the resulting consequences in the context of tumor-cell lysis by native and by interleukin-2-activated (lymphokine-activated killer, LAK*) effector cells. MATERIAL AND METHODS ImmunohistochemistryTissues were snap-frozen and stored in liquid nitrogen and cryostat sections (5-8 µm) were cut for immunohistochemistry and fixed with ethanol/methanol (1:1) for 10 min at room temperature. For immunohistochemistry, the Dako APAAP kit system 40 monoclonal antibodies (MAbs) (Dako, Glostrup, Denmark) was used. Tissue samples were pre-incubated with normal rabbit serum (Sigma, St. Louis, MO) for 20 min. After w...

Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Regulated on Activation Normal T Cell Expressed and Secreted Are Expressed by Human Breast Carcinoma Cells and Support Eosinophil Adhesion and Activation

“…has also been demonstrated to induce ICAM-1 expression on several types of epithelial tumors including breast carcinomas. 29,30,39 In contrast, VCAM-1 has not been examined with respect to induction with TNF-␣; however, in other studies VCAM-1 has not been shown to be expressed by breast carcinoma cells. 14 RT-PCR, Western blotting, and cell surface ELISAs were used to examine adhesion molecule expression on several breast carcinoma cell lines.…”

“…[27][28][29][30] We first used RT-PCR to determine if these cells synthesized mRNA for various adhesion molecules. MDA-MB-435S and MDA-MB-468 cells both constitutively expressed high levels of mRNA for ICAM-1 ( Figure 1A).…”

Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia

“…CD40 triggering of B-CLL cells could upregulate CD80, enhance the functional expression of signal 2 and increase the immunogenicity against allogeneic T cells ( Van den Hove et al, 1997;Buhmann et al, 1999). Furthermore, costimulation of CD80 amplified both CD4 and CD8 T-cell responses against tumour cells (Sule-Suso et al, 1995), and CD54 expression on tumour cells was important for tumour-cell killing, as well as being significant for an effective CD4 and CD8 T-cell activation (Budinsky et al, 1997;Croft et al, 1997). In a murine system, presentation of peptides by naive B cells or by CD54 2 /CD80 2 fibroblasts induced T-cell anergy, while activated B cells or CD54 1 / CD80 1 fibroblasts used as antigen-presenting cells induced T-cell activation (Croft et al, 1997).…”

Expression Profiling after Induction of Demethylation in MCF-7 Breast Cancer Cells Identifies Involvement of TNF-α Mediated Cancer Pathways

“…ICAM1 has been shown to play a role as a cell adhesion molecule and is related to immune responses. TNF-α has been found to reinduce expression of ICAM1, which was downregulated in breast cancer (Budinsky et al, 1997). Significantly downregulated cancerrelevant genes included POSTN (3.0-fold decrease in both 5 and 10 μM Aza treated cells) and NOTCH4 (3.0-fold decrease in 5 μM Aza treated cells and 5.0-fold decrease in 10 μM Aza treated cells).…”