Human epithelial cancers secrete immunoglobulin g with unidentified specificity to promote growth and survival of tumor cells.
Immunoglobulins (Igs) are found thus far only to be produced by differentiated B lymphocytes. By immunohistochemistry analysis, in situ hybridization, and laser capture microdissection-assisted single-cell PCR, we demonstrate that human cancers of epithelial origin, including carcinomas of breast, colon, liver, lung, established epithelial cancer lines, as well as some normal lung tissues, also produce IgG in both cytoplasmic and secreted forms. Furthermore, blockade of tumor-derived IgG by either antisense DNA or antihuman IgG antibody increased programmed cell death and inhibited growth of cancer cells in vitro. More importantly, administration of antihuman IgG antibody also suppressed the growth of an IgG-secreting carcinoma line in immunodeficient nude mice. Our results support a role of tumor-derived IgG as growth factor for epithelial cancers. Prevalent expression of IgG in human carcinomas and its growth-promoting functions may have important implications in growth regulation and targeted therapy of human cancers.
Qiu
Xiaoyan
X
Beijing University Center for Human Disease Genomics, 38 Xue-yuan Road, 100083 Beijing, China. qiuxy@bjmu.edu.cn
Zhu
Xiaohui
X
Zhang
Liang
L
Mao
Yuntao
Y
Zhang
Jian
J
Hao
Peng
P
Li
Guohui
G
Lv
Peng
P
Li
Zhixin
Z
Sun
Xin
X
Wu
Lemeng
L
Zheng
Jie
J
Deng
Yuqing
Y
Hou
Chunmei
C
Tang
Peixian
P
Zhang
Shuren
S
Zhang
Youhui
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D014183:Transplantation, Heterologous
D007074:Immunoglobulin G; D016376:Oligonucleotides, Antisense