Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The melanoma tumor antigen, melanotransferrin (p97): a 25-year hallmark – from iron metabolism to tumorigenesis

Oncogene volume 26, pages 6113–6124 (2007)Cite this article

Abstract

Melanotransferrin (MTf) or melanoma tumor antigen p97 is a transferrin (Tf) homolog that is found predominantly bound to the cell membrane via a glycosyl phosphatidylinositol anchor. The molecule is a member of the Tf superfamily and binds iron through a single high-affinity iron(III)-binding site. Since its discovery on the plasma membrane of melanoma cells, the function of MTf has remained intriguing, particularly in relation to its role in cancer cell iron transport. In fact, considering the crucial role of iron in many metabolic pathways, e.g., DNA synthesis, it was important to understand the function of MTf in the transport of this vital nutrient. MTf has also been implicated in diverse physiological processes, such as plasminogen activation, angiogenesis and cell migration. However, recent studies using a knockout mouse and post-transcriptional gene silencing have demonstrated that MTf is not involved in iron metabolism, but plays a vital role in melanoma cell proliferation and tumorigenesis. In this review, we discuss the possible biological functions of MTf, particularly in relation to cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG et al. (2000). The genome sequence of Drosophila melanogaster. Science 287: 2185–2195.

    Google Scholar 

  • Aledo JC, Segura JA, Medina MA, Alonso FJ, Nunez de Castro I, Marquez J . (1994). Phosphate-activated glutaminase expression during tumor development. FEBS Lett 341: 39–42.

    CAS  PubMed  Google Scholar 

  • Alemany R, Vila MR, Franci C, Egea G, Real FX, Thomson TM . (1993). Glycosyl phosphatidylinositol membrane anchoring of melanotransferrin (p97): apical compartmentalization in intestinal epithelial cells. J Cell Sci 104 (Pt 4): 1155–1162.

    CAS  PubMed  Google Scholar 

  • Andreasen PA, Egelund R, Petersen HH . (2000). The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci 57: 25–40.

    CAS  PubMed  Google Scholar 

  • Andreasen PA, Kjoller L, Christensen L, Duffy MJ . (1997). The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer 72: 1–22.

    CAS  PubMed  Google Scholar 

  • Bailey S, Evans RW, Garratt RC, Gorinsky B, Hasnain S, Horsburgh C et al. (1988). Molecular structure of serum transferrin at 3.3-A resolution. Biochemistry 27: 5804–5812.

    CAS  PubMed  Google Scholar 

  • Baker EN, Baker HM, Smith CA, Stebbins MR, Kahn M, Hellstrom KE et al. (1992). Human melanotransferrin (p97) has only one functional iron-binding site. FEBS Lett 298: 215–218.

    CAS  PubMed  Google Scholar 

  • Baker EN, Lindley PF . (1992). New perspectives on the structure and function of transferrins. J Inorg Biochem 47: 147–160.

    CAS  PubMed  Google Scholar 

  • Beard JL, Connor JR, Jones BC . (1993). Iron in the brain. Nutr Rev 51: 157–170.

    CAS  PubMed  Google Scholar 

  • Birck A, Kirkin AF, Zeuthen J, Hou-Jensen K . (1999). Expression of basic fibroblast growth factor and vascular endothelial growth factor in primary and metastatic melanoma from the same patients. Melanoma Res 9: 375–381.

    CAS  PubMed  Google Scholar 

  • Black BL, Olson EN . (1998). Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins. Annu Rev Cell Dev Biol 14: 167–196.

    CAS  PubMed  Google Scholar 

  • Brown D . (1993). The tyrosine kinase connection: how GPI-anchored proteins activate T cells. Curr Opin Immunol 5: 349–354.

    CAS  PubMed  Google Scholar 

  • Brown D, Waneck GL . (1992). Glycosyl-phosphatidylinositol-anchored membrane proteins. J Am Soc Nephrol 3: 895–906.

    CAS  PubMed  Google Scholar 

  • Brown JP, Hewick RM, Hellstrom I, Hellstrom KE, Doolittle RF, Dreyer WJ . (1982). Human melanoma-associated antigen p97 is structurally and functionally related to transferrin. Nature 296: 171–173.

    CAS  PubMed  Google Scholar 

  • Brown JP, Nishiyama K, Hellstrom I, Hellstrom KE . (1981a). Structural characterization of human melanoma-associated antigen p97 with monoclonal antibodies. J Immunol 127: 539–546.

    CAS  PubMed  Google Scholar 

  • Brown JP, Woodbury RG, Hart CE, Hellstrom I, Hellstrom KE . (1981b). Quantitative analysis of melanoma-associated antigen p97 in normal and neoplastic tissues. Proc Natl Acad Sci USA 78: 539–543.

    CAS  PubMed  Google Scholar 

  • Choong PF, Nadesapillai AP . (2003). Urokinase plasminogen activator system: a multifunctional role in tumor progression and metastasis. Clin Orthop 415: S46–S58.

    Google Scholar 

  • Courey AJ, Holtzman DA, Jackson SP, Tjian R . (1989). Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell 59: 827–836.

    CAS  PubMed  Google Scholar 

  • Danielsen EM, van Deurs B . (1995). A transferrin-like GPI-linked iron-binding protein in detergent-insoluble noncaveolar microdomains at the apical surface of fetal intestinal epithelial cells. J Cell Biol 131: 939–950.

    CAS  PubMed  Google Scholar 

  • Demeule M, Bertrand Y, Michaud-Levesque J, Jodoin J, Rolland Y, Gabathuler R et al. (2003). Regulation of plasminogen activation: a role for melanotransferrin (p97) in cell migration. Blood 102: 1723–1731.

    CAS  PubMed  Google Scholar 

  • Demeule M, Poirier J, Jodoin J, Bertrand Y, Desrosiers RR, Dagenais C et al. (2002). High transcytosis of melanotransferrin (P97) across the blood-brain barrier. J Neurochem 83: 924–933.

    CAS  PubMed  Google Scholar 

  • Denijn M, Ruiter DJ . (1993). The possible role of angiogenesis in the metastatic potential of human melanoma. Clinicopathological aspects. Melanoma Res 3: 5–14.

    CAS  PubMed  Google Scholar 

  • Desrosiers RR, Bertrand Y, Nguyen QT, Demeule M, Gabathuler R, Kennard ML et al. (2003). Expression of melanotransferrin isoforms in human serum: relevance to Alzheimer's disease. Biochem J 374: 463–471.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Duchange N, Ochoa A, Plowman GD, Roze A, Amdjadi M, Zakin MM . (1992). Identification of an enhancer involved in the melanoma-specific expression of the tumor antigen melanotransferrin gene. Nucleic Acids Res 20: 2853–2859.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dunn LL, Sekyere EO, Suryo Rahmanto Y, Richardson DR . (2006). The function of melanotransferrin: a role in melanoma cell proliferation and tumorigenesis. Carcinogenesis 27: 2157–2169.

    CAS  PubMed  Google Scholar 

  • Estin CD, Stevenson U, Kahn M, Hellstrom I, Hellstrom KE . (1989). Transfected mouse melanoma lines that express various levels of human melanoma-associated antigen p97. J Natl Cancer Inst 81: 445–448.

    CAS  PubMed  Google Scholar 

  • Food MR, Rothenberger S, Gabathuler R, Haidl ID, Reid G, Jefferies WA . (1994). Transport and expression in human melanomas of a transferrin-like glycosylphosphatidylinositol-anchored protein. J Biol Chem 269: 3034–3040.

    CAS  PubMed  Google Scholar 

  • Food MR, Sekyere EO, Richardson DR . (2002). The soluble form of the membrane-bound transferrin homologue, melanotransferrin, inefficiently donates iron to cells via nonspecific internalization and degradation of the protein. Eur J Biochem 269: 4435–4445.

    CAS  PubMed  Google Scholar 

  • Furumura M, Potterf SB, Toyofuku K, Matsunaga J, Muller J, Hearing VJ . (2001). Involvement of ITF2 in the transcriptional regulation of melanogenic genes. J Biol Chem 276: 28147–28154.

    CAS  PubMed  Google Scholar 

  • Garratt RC, Jhoti H . (1992). A molecular model for the tumour-associated antigen, p97, suggests a Zn-binding function. FEBS Lett 305: 55–61.

    CAS  PubMed  Google Scholar 

  • Graeven U, Rodeck U, Karpinski S, Jost M, Philippou S, Schmiegel W . (2001). Modulation of angiogenesis and tumorigenicity of human melanocytic cells by vascular endothelial growth factor and basic fibroblast growth factor. Cancer Res 61: 7282–7290.

    CAS  PubMed  Google Scholar 

  • Graham TA, Ferkey DM, Mao F, Kimelman D, Xu W . (2001). Tcf4 can specifically recognize beta-catenin using alternative conformations. Nat Struct Biol 8: 1048–1052.

    CAS  PubMed  Google Scholar 

  • Jefferies WA, Food MR, Gabathuler R, Rothenberger S, Yamada T, Yasuhara O et al. (1996). Reactive microglia specifically associated with amyloid plaques in Alzheimer's disease brain tissue express melanotransferrin. Brain Res 712: 122–126.

    CAS  PubMed  Google Scholar 

  • Kalinowski DS, Richardson DR . (2005). The evolution of iron chelators for the treatment of iron overload disease and cancer. Pharmacol Rev 57: 547–583.

    CAS  PubMed  Google Scholar 

  • Kameyama K, Takezaki S, Kanzaki T, Nishiyama S . (1986). HLA-DR and melanoma-associated antigen (p97) expression during the cell cycle in human melanoma cell lines, and the effects of recombinant gamma-interferon: two-color flow cytometric analysis. J Invest Dermatol 87: 313–318.

    CAS  PubMed  Google Scholar 

  • Kato Y, Matsukawa H, Yoshiwara Y, Oka O, Fujita T . (2001). Method and reagent for assaying arthtritis-associated melanotransferrin. WO/2001/011368.

  • Kawabata H, Tong X, Kawanami T, Wano Y, Hirose Y, Sugai S et al. (2004). Analyses for binding of the transferrin family of proteins to the transferrin receptor 2. Br J Haematol 127: 464–473.

    CAS  PubMed  Google Scholar 

  • Kawamoto T, Pan H, Yan W, Ishida H, Usui E, Oda R et al. (1998). Expression of membrane-bound transferrin-like protein p97 on the cell surface of chondrocytes. Eur J Biochem 256: 503–509.

    CAS  PubMed  Google Scholar 

  • Kennard ML, Feldman H, Yamada T, Jefferies WA . (1996). Serum levels of the iron binding protein p97 are elevated in Alzheimer's disease. Nat Med 2: 1230–1235.

    CAS  PubMed  Google Scholar 

  • Kennard ML, Richardson DR, Gabathuler R, Ponka P, Jefferies WA . (1995). A novel iron uptake mechanism mediated by GPI-anchored human p97. EMBO J 14: 4178–4186.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim DK, Seo MY, Lim SW, Kim S, Kim JW, Carroll BJ et al. (2001). Serum melanotransferrin, p97 as a biochemical marker of Alzheimer's disease. Neuropsychopharmacology 25: 84–90.

    CAS  PubMed  Google Scholar 

  • Kvamme E, Roberg B, Torgner IA . (2000). Phosphate-activated glutaminase and mitochondrial glutamine transport in the brain. Neurochem Res 25: 1407–1419.

    CAS  PubMed  Google Scholar 

  • Kwok JC, Richardson DR . (2002). The iron metabolism of neoplastic cells: alterations that facilitate proliferation? Crit Rev Oncol Hematol 42: 65–78.

    PubMed  Google Scholar 

  • Lambert LA, Perri H, Halbrooks PJ, Mason AB . (2005a). Evolution of the transferrin family: conservation of residues associated with iron and anion binding. Comp Biochem Physiol B Biochem Mol Biol 142: 129–141.

    PubMed  Google Scholar 

  • Lambert LA, Perri H, Meehan TJ . (2005b). Evolution of duplications in the transferrin family of proteins. Comp Biochem Physiol B Biochem Mol Biol 140: 11–25.

    PubMed  Google Scholar 

  • Le Beau MM, Diaz MO, Plowman GD, Brown JP, Rowley JD . (1986). Chromosomal sublocalization of the human p97 melanoma antigen. Hum Genet 72: 294–296.

    CAS  PubMed  Google Scholar 

  • Liao SK . (1996). Identification with monoclonal antibody 140.240 of a structural variant of melanotransferrin shed by human melanoma cell lines in vitro. Anticancer Res 16: 171–176.

    CAS  PubMed  Google Scholar 

  • Lisanti MP, Caras IW, Davitz MA, Rodriguez-Boulan E . (1989). A glycophospholipid membrane anchor acts as an apical targeting signal in polarized epithelial cells. J Cell Biol 109: 2145–2156.

    CAS  PubMed  Google Scholar 

  • Lisanti MP, Le Bivic A, Saltiel AR, Rodriguez-Boulan E . (1990). Preferred apical distribution of glycosyl-phosphatidylinositol (GPI) anchored proteins: a highly conserved feature of the polarized epithelial cell phenotype. J Membr Biol 113: 155–167.

    CAS  PubMed  Google Scholar 

  • Loertscher R, Lavery P . (2002). The role of glycosyl phosphatidyl inositol (GPI)-anchored cell surface proteins in T-cell activation. Transpl Immunol 9: 93–96.

    CAS  PubMed  Google Scholar 

  • Low MG . (1989). The glycosyl-phosphatidylinositol anchor of membrane proteins. Biochim Biophys Acta 988: 427–454.

    CAS  PubMed  Google Scholar 

  • Low MG, Huang KS . (1991). Factors affecting the ability of glycosylphosphatidylinositol-specific phospholipase D to degrade the membrane anchors of cell surface proteins. Biochem J 279 (Part 2): 483–493.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mann B, Gelos M, Siedow A, Hanski ML, Gratchev A, Ilyas M et al. (1999). Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci USA 96: 1603–1608.

    CAS  PubMed  Google Scholar 

  • McKinsey TA, Zhang CL, Olson EN . (2002). MEF2: a calcium-dependent regulator of cell division, differentiation and death. Trends Biochem Sci 27: 40–47.

    CAS  PubMed  Google Scholar 

  • McNagny KM, Rossi F, Smith G, Graf T . (1996). The eosinophil-specific cell surface antigen, EOS47, is a chicken homologue of the oncofetal antigen melanotransferrin. Blood 87: 1343–1352.

    CAS  PubMed  Google Scholar 

  • Medina MA, Sanchez-Jimenez F, Marquez J, Rodriguez Quesada A, Nunez de Castro I . (1992). Relevance of glutamine metabolism to tumor cell growth. Mol Cell Biochem 113: 1–15.

    CAS  PubMed  Google Scholar 

  • Metz CN, Schenkman S, Davitz MA . (1991). Characterization of the plasma glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD). Cell Biol Int Rep 15: 875–882.

    CAS  PubMed  Google Scholar 

  • Michaud-Levesque J, Demeule M, Beliveau R . (2005). Stimulation of cell surface plasminogen activation by membrane-bound melanotransferrin: a key phenomenon for cell invasion. Exp Cell Res 308: 479–490.

    CAS  PubMed  Google Scholar 

  • Michaud-Levesque J, Demeule M, Beliveau R . (2006). In vivo inhibition of angiogenesis by a soluble form of melanotransferrin. Carcinogenesis 28: 280–288.

    PubMed  Google Scholar 

  • Miyata T, Yamada N, Iida Y, Nishimura J, Takeda J, Kitani T et al. (1994). Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 330: 249–255.

    CAS  PubMed  Google Scholar 

  • Montgomery AM, De Clerck YA, Langley KE, Reisfeld RA, Mueller BM . (1993). Melanoma-mediated dissolution of extracellular matrix: contribution of urokinase-dependent and metalloproteinase-dependent proteolytic pathways. Cancer Res 53: 693–700.

    CAS  PubMed  Google Scholar 

  • Morgan EH . (1981). Transferrin biochemistry, physiology and clinical significance. Mol Aspects Med 4: 1–123.

    Google Scholar 

  • Moroo I, Ujiie M, Walker BL, Tiong JW, Vitalis TZ, Karkan D et al. (2003). Identification of a novel route of iron transcytosis across the mammalian blood-brain barrier. Microcirculation 10: 457–462.

    CAS  PubMed  Google Scholar 

  • Nakamasu K, Kawamoto T, Shen M, Gotoh O, Teramoto M, Noshiro M et al. (1999). Membrane-bound transferrin-like protein (MTf): structure, evolution and selective expression during chondrogenic differentiation of mouse embryonic cells. Biochim Biophys Acta 1447: 258–264.

    CAS  PubMed  Google Scholar 

  • Nakamasu K, Kawamoto T, Yoshida E, Noshiro M, Matsuda Y, Kato Y . (2001). Structure and promoter analysis of the mouse membrane-bound transferrin-like protein (MTf) gene. Eur J Biochem 268: 1468–1476.

    CAS  PubMed  Google Scholar 

  • Nappi AJ, Vass E . (2000). Iron, metalloenzymes and cytotoxic reactions. Cell Mol Biol (Noisy-le-grand) 46: 637–647.

    CAS  Google Scholar 

  • Natali PG, Roberts JT, Difilippo F, Bigotti A, Dent PB, Ferrone S et al. (1987). Immunohistochemical detection of antigen in human primary and metastatic melanomas by the monoclonal antibody 140.240 and its possible prognostic significance. Cancer 59: 55–63.

    CAS  PubMed  Google Scholar 

  • Naya FJ, Black BL, Wu H, Bassel-Duby R, Richardson JA, Hill JA et al. (2002). Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Nat Med 8: 1303–1309.

    CAS  PubMed  Google Scholar 

  • Neckers LM, Cossman J . (1983). Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci USA 80: 3494–3498.

    CAS  PubMed  Google Scholar 

  • Neitzel LT, Neitzel CD, Magee KL, Malafa MP . (1999). Angiogenesis correlates with metastasis in melanoma. Ann Surg Oncol 6: 70–74.

    CAS  PubMed  Google Scholar 

  • Pan W, Kastin AJ, Zankel TC, van Kerkhof P, Terasaki T, Bu G . (2004). Efficient transfer of receptor-associated protein (RAP) across the blood-brain barrier. J Cell Sci 117: 5071–5078.

    CAS  PubMed  Google Scholar 

  • Plowman GD, Brown JP, Enns CA, Schroder J, Nikinmaa B, Sussman HH et al. (1983). Assignment of the gene for human melanoma-associated antigen p97 to chromosome 3. Nature 303: 70–72.

    CAS  PubMed  Google Scholar 

  • Ribatti D, Vacca A, Palma W, Lospalluti M, Dammacco F . (1992). Angiogenesis during tumor progression in human malignant melanoma. Exs 61: 415–420.

    CAS  PubMed  Google Scholar 

  • Richardson D, Baker E . (1991a). The uptake of inorganic iron complexes by human melanoma cells. Biochim Biophys Acta 1093: 20–28.

    CAS  PubMed  Google Scholar 

  • Richardson D, Baker E . (1992a). Two mechanisms of iron uptake from transferrin by melanoma cells. The effect of desferrioxamine and ferric ammonium citrate. J Biol Chem 267: 13972–13979.

    CAS  PubMed  Google Scholar 

  • Richardson DR . (2000). The role of the membrane-bound tumour antigen, melanotransferrin (p97), in iron uptake by the human malignant melanoma cell. Eur J Biochem 267: 1290–1298.

    CAS  PubMed  Google Scholar 

  • Richardson DR, Baker E . (1990). The uptake of iron and transferrin by the human malignant melanoma cell. Biochim Biophys Acta 1053: 1–12.

    CAS  PubMed  Google Scholar 

  • Richardson DR, Baker E . (1991b). The release of iron and transferrin from the human melanoma cell. Biochim Biophys Acta 1091: 294–302.

    CAS  PubMed  Google Scholar 

  • Richardson DR, Baker E . (1992b). Intermediate steps in cellular iron uptake from transferrin. Detection of a cytoplasmic pool of iron, free of transferrin. J Biol Chem 267: 21384–21389.

    CAS  PubMed  Google Scholar 

  • Richardson DR, Baker E . (1994). Two saturable mechanisms of iron uptake from transferrin in human melanoma cells: the effect of transferrin concentration, chelators, and metabolic probes on transferrin and iron uptake. J Cell Physiol 161: 160–168.

    CAS  PubMed  Google Scholar 

  • Richardson DR, Morgan EH . (2004). The transferrin homologue, melanotransferrin (p97), is rapidly catabolized by the liver of the rat and does not effectively donate iron to the brain. Biochim Biophys Acta 1690: 124–133.

    CAS  PubMed  Google Scholar 

  • Richardson DR, Ponka P . (1997). The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim Biophys Acta 1331: 1–40.

    CAS  PubMed  Google Scholar 

  • Rose TM, Plowman GD, Teplow DB, Dreyer WJ, Hellstrom KE, Brown JP . (1986). Primary structure of the human melanoma-associated antigen p97 (melanotransferrin) deduced from the mRNA sequence. Proc Natl Acad Sci USA 83: 1261–1265.

    CAS  PubMed  Google Scholar 

  • Rothenberger S, Food MR, Gabathuler R, Kennard ML, Yamada T, Yasuhara O et al. (1996). Coincident expression and distribution of melanotransferrin and transferrin receptor in human brain capillary endothelium. Brain Res 712: 117–121.

    CAS  PubMed  Google Scholar 

  • Roze-Heusse A, Houbiguian ML, Debacker C, Zakin MM, Duchange N . (1996). Melanotransferrin gene expression in melanoma cells is correlated with high levels of Jun/Fos family transcripts and with the presence of a specific AP1-dependent ternary complex. Biochem J 318 (Part 3): 883–888.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Saffer JD, Jackson SP, Annarella MB . (1991). Developmental expression of Sp1 in the mouse. Mol Cell Biol 11: 2189–2199.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sala R, Jefferies WA, Walker B, Yang J, Tiong J, Law SK et al. (2002). The human melanoma associated protein melanotransferrin promotes endothelial cell migration and angiogenesis in vivo. Eur J Cell Biol 81: 599–607.

    CAS  PubMed  Google Scholar 

  • Sargiacomo M, Sudol M, Tang Z, Lisanti MP . (1993). Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J Cell Biol 122: 789–807.

    CAS  PubMed  Google Scholar 

  • Sciot R, de Vos R, van Eyken P, van der Steen K, Moerman P, Desmet VJ . (1989). In situ localization of melanotransferrin (melanoma-associated antigen P97) in human liver. A light- and electronmicroscopic immunohistochemical study. Liver 9: 110–119.

    CAS  PubMed  Google Scholar 

  • Sekyere E, Dunn LL, Richardson DR . (2003). The double-edged nature of using genetic databases: melanotransferrin genes and transcripts. FEBS Lett 547: 233.

    CAS  PubMed  Google Scholar 

  • Sekyere E, Food MR, Richardson DR . (2002). A second melanotransferrin gene (MTf2) and a novel protein isoform: explanation for the membrane-bound and soluble forms of melanotransferrin? FEBS Lett 512: 350–352.

    CAS  PubMed  Google Scholar 

  • Sekyere E, Richardson DR . (2000). The membrane-bound transferrin homologue melanotransferrin: roles other than iron transport? FEBS Lett 483: 11–16.

    CAS  PubMed  Google Scholar 

  • Sekyere EO, Dunn LL, Rahmanto YS, Richardson DR . (2006). Role of melanotransferrin in iron metabolism: studies using targeted gene disruption in-vivo. Blood 107: 2599–2601.

    CAS  PubMed  Google Scholar 

  • Sekyere EO, Dunn LL, Richardson DR . (2005). Examination of the distribution of the transferrin homologue, melanotransferrin (tumour antigen p97), in mouse and human. Biochim Biophys Acta 1722: 131–142.

    CAS  PubMed  Google Scholar 

  • Seligman PA, Butler CD, Massey EJ, Kaur JA, Brown JP, Plowman GD et al. (1986). The p97 antigen is mapped to the q24-qter region of chromosome 3; the same region as the transferrin receptor. Am J Hum Genet 38: 540–548.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sharom FJ, Lehto MT . (2002). Glycosylphosphatidylinositol-anchored proteins: structure, function, and cleavage by phosphatidylinositol-specific phospholipase C. Biochem Cell Biol 80: 535–549.

    CAS  PubMed  Google Scholar 

  • Stahl A, Mueller BM . (1994). Binding of urokinase to its receptor promotes migration and invasion of human melanoma cells in vitro. Cancer Res 54: 3066–3071.

    CAS  PubMed  Google Scholar 

  • Suardita K, Fujimoto K, Oda R, Shimazu A, Miyazaki K, Kawamoto T et al. (2002). Effects of overexpression of membrane-bound transferrin-like protein (MTf) on chondrogenic differentiation in vitro. J Biol Chem 277: 48579–48586.

    CAS  PubMed  Google Scholar 

  • Sugimoto K, Simard J, Haagensen DE, Labrie F . (1994). Inverse relationships between cell proliferation and basal or androgen-stimulated apolipoprotein D secretion in LNCaP human prostate cancer cells. J Steroid Biochem Mol Biol 51: 167–174.

    CAS  PubMed  Google Scholar 

  • Terrisse L, Poirier J, Bertrand P, Merched A, Visvikis S, Siest G et al. (1998). Increased levels of apolipoprotein D in cerebrospinal fluid and hippocampus of Alzheimer's patients. J Neurochem 71: 1643–1650.

    CAS  PubMed  Google Scholar 

  • Ware RE, Nishimura J, Moody MA, Smith C, Rosse WF, Howard TA . (1998). The PIG-A mutation and absence of glycosylphosphatidylinositol-linked proteins do not confer resistance to apoptosis in paroxysmal nocturnal hemoglobinuria. Blood 92: 2541–2550.

    CAS  PubMed  Google Scholar 

  • Woodbury RG, Brown JP, Yeh MY, Hellstrom I, Hellstrom KE . (1980). Identification of a cell surface protein, p97, in human melanomas and certain other neoplasms. Proc Natl Acad Sci USA 77: 2183–2187.

    CAS  PubMed  Google Scholar 

  • Yamada T, Tsujioka Y, Taguchi J, Takahashi M, Tsuboi Y, Moroo I et al. (1999). Melanotransferrin is produced by senile plaque-associated reactive microglia in Alzheimer's disease. Brain Res 845: 1–5.

    CAS  PubMed  Google Scholar 

  • Yang F, Lum JB, McGill JR, Moore CM, Naylor SL, van Bragt PH et al. (1984). Human transferrin: cDNA characterization and chromosomal localization. Proc Natl Acad Sci USA 81: 2752–2756.

    CAS  PubMed  Google Scholar 

  • Zhao M, New L, Kravchenko VV, Kato Y, Gram H, di Padova F et al. (1999). Regulation of the MEF2 family of transcription factors by p38. Mol Cell Biol 19: 21–30.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We acknowledge the critical comments on the manuscript before submission by Dr Dong Fu, Dr David Lovejoy, Dr Robert Sutak and Ms Danuta Kalinowski. This work was supported by a fellowship and projects grant from the National Health and Medical Research Council of Australia (NHMRC) and a Discovery Grant from the Australian Research Council (ARC) to DRR. YSR acknowledges a PhD Scholarship from the Australian Post-Graduate Award Scheme, University of Sydney, and LLD acknowledges a Dora Lush PhD Scholarship from the NHMRC.

Author information

Authors and Affiliations

  1. Department of Pathology, Iron Metabolism and Chelation Program, University of Sydney, Sydney, New South Wales, Australia

    Y Suryo Rahmanto, L L Dunn & D R Richardson

Authors
  1. Y Suryo Rahmanto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L L Dunn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D R Richardson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D R Richardson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suryo Rahmanto, Y., Dunn, L. & Richardson, D. The melanoma tumor antigen, melanotransferrin (p97): a 25-year hallmark – from iron metabolism to tumorigenesis. Oncogene 26, 6113–6124 (2007). https://doi.org/10.1038/sj.onc.1210442

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210442

Keywords

This article is cited by

Search

Advanced search

Quick links