title: Loss of expression of the recycling receptor, FcRn, promotes tumor cell growth by increasing albumin consumption.
abstract: Tumor cells rely on high concentrations of amino acids to support their growth and proliferation. Although increased macropinocytic uptake and lysosomal degradation of the most abundant serum protein, albumin, in Ras-transformed cells can meet these demands, it is not understood how the majority of tumor cells that express wild type Ras achieve this. In the current study we reveal that the neonatal Fc receptor, FcRn, regulates tumor cell proliferation through the ability to recycle its ligand, albumin. By contrast with normal epithelial cells, we show that human FcRn is present at very low or undetectable levels in the majority of tumor cell lines analyzed. Remarkably, shRNA-mediated ablation of FcRn expression in an FcRn-positive tumor cell line results in a substantial growth increase of tumor xenografts, whereas enforced expression of this receptor by lentiviral transduction has the reverse effect. Moreover, intracellular albumin and glutamate levels are increased by the loss of FcRn-mediated recycling of albumin, combined with hypoalbuminemia in tumor-bearing mice. These studies identify a novel role for FcRn as a suppressor of tumor growth and have implications for the use of this receptor as a prognostic indicator and therapeutic target.
authors.affiliation: Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA.|Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
authors.forename: Rafal
authors.initials: R
authors.lastname: Swiercz
authors.affiliation: Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA.|Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Mo
authors.affiliation: Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA.|Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Khare
authors.affiliation: Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA.|Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
authors.forename: Zita
authors.initials: Z
authors.lastname: Schneider
authors.affiliation: Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA.|Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Raimund J
authors.initials: RJ
authors.lastname: Ober
authors.affiliation: Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA.|Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
authors.forename: Elizabeth Sally
authors.initials: ES
authors.lastname: Ward
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D064593:Heterografts; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011961:Receptors, Fc / Q000235:genetics* / Q000378:metabolism; D012709:Serum Albumin / Q000235:genetics* / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; D012709:Serum Albumin; C100688:Fc receptor, neonatal
keywords: albumin; hypoalbuminemia; neonatal Fc receptor (FcRn); recycling receptor; tumor suppressor