Decreased expression of ICAM‐1 and its induction by tumor necrosis factor on breast‐cancer cells in vitro

• Published in: International journal of cancer 1997-06, Vol.71 (6), p.1086-1090
• Main Authors: Budinsky, Alexandra C., Brodowicz, Thomas, Wiltschke, Christoph, Czerwenka, Klaus, Michl, Ilse, Krainer, Michael, Zielinski, Christoph C.
• Format: Article
• Language: English
• Subjects: Antibodies - immunology; Biological and medical sciences; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1 - biosynthesis; Intercellular Adhesion Molecule-1 - metabolism; Killer Cells, Lymphokine-Activated - immunology; Mammary gland diseases; Medical sciences; Receptors, Tumor Necrosis Factor - immunology; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19970611)71:6<1086::AID-IJC27>3.0.CO;2-A

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, β1‐integrin and β3‐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‐α), interleukin 2 (IL‐2), granulocyte/macrophage‐colony‐stimulating‐factor (GM‐CSF), interferon‐alpha (IFN‐α) and interferon‐gamma (IFN‐γ), 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. Int. J. Cancer 71: 1086‐1090, 1997. © 1997 Wiley‐Liss Inc.