Aberrant high expression of immunoglobulin G in epithelial stem/progenitor-like cells contributes to tumor initiation and metastasis
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Qinyuan Liao1,2,*, Wei Liu1,2,*, Yang Liu1,2,*, Fulin Wang4, Chong Wang1,2, Jingxuan Zhang3, Ming Chu1,2, Dongyang Jiang1,2, Lin Xiao1,2, Wenwei Shao1,2, Zhengzuo Sheng1, Xia Tao5, Lei Huo6, C. Cameron Yin7, Youhui Zhang8, Gregory Lee9, Jing Huang1,2, Zihai Li10, Xiaoyan Qiu1,2,3
1Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
2Peking University Center for Human Disease Genomics, Beijing, 100191, China
3Key Laboratory of Medical Immunology, Ministry of Health, Beijing, 100191, China
4Department of Pathology, Chinese PLA General Hospital, Beijing, 100853, China
5Department of Gynecology, Peking University First Hospital, Beijing, 100034, China
6Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA
7Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA
8Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Science, Beijing, 100021, China
9Andrology Lab, University of British Columbia Centre for Reproductive Health, Vancouver, BC V5Z 4H4, Canada
10Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA
*These authors have contributed equally to this work
Xiaoyan Qiu, e-mail: [email protected]
Keywords: IgG, RP215, epithelial stem/progenitor-like cells, tumor metastasis
Received: July 05, 2015 Accepted: October 02, 2015 Published: October 12, 2015
High expression of immunoglobulin G (IgG) in many non-B cell malignancies and its non-conventional roles in promoting proliferation and survival of cancer cells have been demonstrated. However, the precise function of non-B IgG remains incompletely understood. Here we define the antigen specificity of RP215, a monoclonal antibody that specifically recognizes the IgG in cancer cells. Using RP215, our study shows that IgG is overexpressed in cancer cells of epithelial lineage, especially cells with cancer stem/progenitor cell-like features. The RP215-recognized IgG is primarily localized on the cell surface, particularly lamellipodia-like structures. Cells with high IgG display higher migration, increased invasiveness and metastasis, and enhanced self-renewal and tumorgenecity ability in vitro and in vivo. Importantly, depletion of IgG in breast cancer leads to reduced adhesion, invasion and self-renewal and increased apoptosis of cancer cells. We conclude that high expression of IgG is a novel biomarker of tumor progression, metastasis and cancer stem cell maintenance and demonstrate the potential therapeutic benefits of RP215-recognized IgG targeted strategy.
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