Promotion of cell proliferation and inhibition of ADCC by cancerous immunoglobulin expressed in cancer cell lines

Ming Li, Hui Zheng, Zhi Duan, Haidan Liu, Duosha Hu, Ann Bode, Zigang Dong, Ya Cao

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

To explore the significance of cancerous immunoglobulin (Ig) in cancer cell growth, HeLa cervical cancer cells were stably transfected with small interfering RNA (siRNA) that specifically, efficiently and consistently silences the expression of heavy chain genes of all immunoglobulin isotypes. This stable cell line was used to examine cell viability, colony formation and tumor growth in athymic nude mice. The results of these experiments indicated that siRNA-mediated knockdown of cancerous Ig inhibited cell growth in vitro and suppressed tumor cell growth in immune-deficient nude mice in vivo. Similarly, this siRNA also inhibited the growth of MGC gastric cancer cells and MCF-7 breast cancer cells. Furthermore, the presence of cancerous Ig specifically reduced antibody-dependent cell-mediated cytotoxicity (ADCC) induced by an anti-human epithelial growth factor receptor (EGFR) antibody in a dose-dependent manner, suggesting that the cancerous Ig-Fc receptor interaction inhibits natural killer cell (or NK cell) effector function. The prevalent expression of Ig in human carcinomas and its capacity to promote growth and inhibit immunity might have important implications in growth regulation and targeted therapy for human cancers.

Original languageEnglish (US)
Pages (from-to)54-61
Number of pages8
JournalCellular and Molecular Immunology
Volume9
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • antibody-dependent cell-mediated cytotoxicity (ADCC)
  • cancerous immunoglobulin
  • cell proliferation
  • small interfering RNA (siRNA)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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