title: Aberrant high expression of immunoglobulin G in epithelial stem/progenitor-like cells contributes to tumor initiation and metastasis.
abstract: 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.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Fulin
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Beijing, 100191, China.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Zhengzuo
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Department of Gynecology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Tao
authors.affiliation: Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Huo
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
authors.affiliation: Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Science, Beijing, 100021, China.
authors.forename: Youhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Andrology Laboratory, University of British Columbia Centre for Reproductive Health, Vancouver, BC V5Z 4H4, Canada.
authors.forename: Gregory
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Zihai
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Peking University Center for Human Disease Genomics, Beijing, 100191, China.|Key Laboratory of Medical Immunology, Ministry of Health, Beijing, 100191, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: IgG; RP215; epithelial stem/progenitor-like cells; tumor metastasis