LIGHT stimulates IFNγ-mediated intercellular adhesion molecule-1 upregulation of cancer cells

Manchao Zhang, Ribo Guo, Yifan Zhai, Xin Yuan Fu, Dajun Yang

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Intercellular adhesion molecule-1 (ICAM-1) works as one of the ligands for activating the killing activity of natural killer (NK) cells and cancer specific cytotoxic T lymphocytes (CTL). Expression of ICAM-1 enhances lymphocyte adhesion to the cancer cells in vivo. Cancer cell lines express significantly lower level of ICAM-1 than that of normal epithelium or benign cells. Overexpression of LIGHT (LIGHT: homologous to lymphotoxins, indicating inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator [HVEM/TR2]) in MDA-MB-231 human breast cancer cells was observed to suppress tumor growth in vivo. In order to elucidate the mechanisms how LIGHT overexpression could trigger tumor suppression, the expression level of a panel of cell surface makers CD54, CD56, CD95, and CD119 was investigated in a group of cancer cells. Flow cytometry analysis results demonstrate that LIGHT gene expression in cancer cells can greatly increase ICAM-1 expression level, IFNγ alone can stimulate cancer cells to express ICAM-1, which can be highly augmented by LIGHT in a dose-dependent manner. This upregulation of ICAM-1 expression is not only at ICAM-1 protein trafficking level on cell surface as demonstrated by flow cytometry analysis, but also at ICAM-1 total protein level as confirmed by Western blot. There is no difference of expression level among these cancer cell lines for the other three cell surface markers: CD56, CD95 (Fas), and CD119. It was confirmed that LIGHT enhancement upregulation of ICAM-1 expression is at least STAT1 and JAK1 dependent by using STAT1-deficient U3A and JAK1-deficient E2A4 cells. These findings suggest that LIGHT-induced inhibition of tumor growth is highly correlated with its upregulation of ICAM-1 expression.

Original languageEnglish (US)
Pages (from-to)416-426
Number of pages11
JournalHuman Immunology
Volume64
Issue number4
DOIs
StatePublished - Apr 1 2003

Keywords

  • IFN-γ
  • Intercellular adhesion molecule-1 (ICAM-1)
  • LIGHT
  • TNF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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