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Human Epithelial Cancers Secrete Immunoglobulin G with Unidentified Specificity to Promote Growth and Survival of Tumor Cells¹

Beijing University Center for Human Disease Genomics, 100083 Beijing [X. Q., X. Z., L. Z., Y. M., Jia. Zha., P. H., G. L., P. L., Z. L., X. S., L. W., Jie Zhe., Y. D.]; Institute of Basic Medical Science, Academy of Military Medical Science, 100850 Beijing [C. H., P. T.]; and Department of Immunology, Cancer Institute, Chinese Academy of Medical Science and Peking Union Medical College, 10021 Beijing [S. Z., Y. Z.], China

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.

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