title: Transferrin receptor 2 is frequently expressed in human cancer cell lines.
abstract: Different proteins ensure the fine control of iron metabolism at the level of various tissues. Among these proteins, it was discovered a second transferrin receptor (TfR2), that seems to play a key role in the regulation of iron homeostasis. Its mutations are responsible for type 3 hemochromatosis (Type 3 HH). Although TfR2 expression in normal tissues was restricted at the level of liver and intestine, we observed that TfR2 was frequently expressed in tumor cell lines. Particularly frequent was its expression in ovarian cancer, colon cancer and glioblastoma cell lines; less frequent was its expression in leukemic and melanoma cell lines. Interestingly, in these tumor cell lines, TfR2 expression was inversely related to that of receptor 1 for transferrin (TfR1). Experiments of in vitro iron loading or iron deprivation provided evidence that TfR2 is modulated in cancer cell lines according to cellular iron levels following two different mechanisms: (i) in some cells, iron loading caused a downmodulation of total TfR2 levels; (ii) in other cell types, iron loading caused a downmodulation of membrane-bound TfR2, without affecting the levels of total cellular TfR2 content. Iron deprivation caused in both conditions an opposite effect compared to iron loading. These observations suggest that TfR2 expression may be altered in human cancers and warrant further studies in primary tumors. Furthermore, our studies indicate that, at least in tumor cells, TfR2 expression is modulated by iron through different biochemical mechanisms, whose molecular basis remains to be determined.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Calzolari
authors.forename: Isabella
authors.initials: I
authors.lastname: Oliviero
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Gualtiero
authors.initials: G
authors.lastname: Mariani
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffoni
authors.forename: Nadia Maria
authors.initials: NM
authors.lastname: Sposi
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Cesare
authors.initials: C
authors.lastname: Peschle
authors.forename: Ugo
authors.initials: U
authors.lastname: Testa
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018922:HL-60 Cells; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011990:Receptors, Transferrin / Q000096:biosynthesis* / Q000235:genetics; D020298:U937 Cells
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D007501:Iron