Promotion of cell proliferation and inhibition of ADCC by cancerous immunoglobulin expressed in cancer cell lines.
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.
Key Laboratory of Ministry of Education, Key Laboratory of Ministry of Health, Laboratory of Tumor Molecular Biology, Cancer Research Institute, Central South University, Xiangya Road #110, Changsha, China.
Ming
M
Li
Hui
H
Zheng
Zhi
Z
Duan
Haidan
H
Liu
Duosha
D
Hu
Ann
A
Bode
Zigang
Z
Dong
Ya
Y
Cao
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004306:Dose-Response Relationship, Immunologic; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology; D014183:Transplantation, Heterologous; D019139:Tumor Escape / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
D000912:Antibodies, Neoplasm; D034741:RNA, Small Interfering; D011961:Receptors, Fc; C512478:EGFR protein, human; D066246:ErbB Receptors