A novel iron uptake mechanism mediated by GPI-anchored human p97.

Kennard, Malcolm L.; Richardson, Des R.; Gabathuler, Reinhard; Ponka, Prem; Jefferies, Wilfred A.

doi:10.1002/j.1460-2075.1995.tb00091.x

Cited by 97 publications

(84 citation statements)

References 58 publications

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“…These CHO cells expressed 1.2 Â 10 6 MTf molecules per cell, a level three-to four-fold higher than that of the most highly expressing, naturally-derived melanoma cell line, SK-MEL-28 (300-380 000 sites/cell; Brown et al, 1981a;Sekyere and Richardson, 2000). However, after an incubation of 240 min, the Fe uptake from 59 Fe-citrate was only 2.4 times greater than the control CHO cells not expressing MTf (Kennard et al, 1995). Furthermore, hyper-expression of MTf did not result in any increase in Fe uptake from Tf when compared with control cells (Kennard et al, 1995).…”

Section: Functional Role Of Mtf: Melanoma Iron Transport and Metabolismmentioning

confidence: 96%

“…It is of interest to note that Kennard et al (1995) showed that MTf-transfected Chinese hamster ovary (CHO) cells could internalize Fe from Fe(III) citrate complexes. These CHO cells expressed 1.2 Â 10 6 MTf molecules per cell, a level three-to four-fold higher than that of the most highly expressing, naturally-derived melanoma cell line, SK-MEL-28 (300-380 000 sites/cell; Brown et al, 1981a;Sekyere and Richardson, 2000).…”

Section: Functional Role Of Mtf: Melanoma Iron Transport and Metabolismmentioning

confidence: 99%

“…The most obvious difference between MTf and serum Tf is that MTf is bound mainly to the cell membrane by a glycosyl phosphatidylinositol (GPI) anchor, whereas Tf is found free in the plasma (Alemany et al, 1993;Food et al, 1994;Kennard et al, 1995;Nakamasu et al, 1999;Yamada et al, 1999). The sMTf may also be secreted from cells, although at very low levels (Food et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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

2007

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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 posttranscriptional 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.

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Section: Functional Role Of Mtf: Melanoma Iron Transport and Metabolismmentioning

confidence: 96%

Section: Functional Role Of Mtf: Melanoma Iron Transport and Metabolismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2007

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“…Other mechanisms may be involved in Fe acquisition from transferrin by some cell types (17)(18)(19)(20)(21)(22)(23)(24). In most studies the mechanism responsible remains ill defined.…”

mentioning

confidence: 99%

“…However, a pathway involving the intracellular protein mobilferrin in conjunction with membrane integrins has been described (21,22). Melanotransferrin, a plasma membrane-associated Fe-binding protein in human melanoma and other cell lines, has also been implicated in some forms of Fe acquisition from transferrin (23,24). These processes do not appear to require transferrin internalization.…”

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confidence: 99%

Multivalent Metal-Induced Iron Acquisition from Transferrin and Lactoferrin by Myeloid Cells

Olakanmi

Rasmussen

Lewis

et al. 2002

The Journal of Immunology

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We previously described a unique, high-capacity, ATP-independent mechanism through which myeloid cells acquire Fe from low-m.w. chelates. The rate of this Fe acquisition is markedly increased by cellular exposure to multivalent metal cations. Because most Fe in vivo is bound to transferrin or lactoferrin, we examined whether this mechanism also contributes to myeloid cell acquisition of Fe from transferrin and/or lactoferrin. Using HL-60 cells as a model system, we show cellular acquisition of 59Fe from both lactoferrin and transferrin that was unaffected by conditions that depleted the cells of ATP or disrupted their cytoskeleton. Fe acquisition was dramatically increased by cell exposure to various metals including Ga3+, Gd3+, Al3+, Fe3+, La3+, Zr4+, Sn4+, Cu2+, and Zn2+ by a process that was reversible. Exposure to these same metals also increased binding of both transferrin and lactoferrin to the cell surface by a process that does not appear to involve the well-described plasma membrane receptor for transferrin. Approximately 60% of the Fe acquired by the cells from transferrin and lactoferrin remained cell associated 18 h later. HL-60 cells possess a high-capacity multivalent metal-inducible mechanism for Fe acquisition from transferrin and lactoferrin that bears many similarities to the process previously described that allows these and other cell types to acquire Fe from low-m.w. Fe chelates. The biologic importance of this mechanism may relate to its high Fe acquisition capacity and the speed with which it is able to rapidly adapt to the level of extracellular Fe.

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Expression of cell surface GPI-anchored human p97 in baculovirus-infected insect cells

Kennard

Shimizu

Gabathuler

et al. 1997

Biotechnol. Bioeng.

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The baculovirus/insect cell system (Autographa californica multiple nuclear polyhedrosis virus/Spodoptera frugiperda Sf9 cells) was used to express the GPI‐anchored human melanoma tumor antigen, melanotransferrin or p97. This system served to study the expression and productivity of recombinant GPI‐anchored p97 by insect cells. The Sf9 cells expressed a cell surface GPI‐anchored form of p97 as well as a soluble form of p97 that did not appear to be derived from the GPI‐anchored form of p97. Both recombinant forms, although Endo H resistant, migrated slightly faster (∼88 kDa) than the native p97 (∼95–97 kDa). The insect GPI‐anchored p97 was sensitive to PI‐PLC, which exposed a detectable cross‐reacting determinant. The Sf9 cell surface p97 expression was similar to that of human melanoma (SK‐MEL‐28) cells, whereas the Sf9 cell specific secretion rate was 10‐fold higher. Also Sf9 cells retained considerably higher levels of p97 within the cell. The Sf9 cell surface expression of p97 varied with time after infection, with the maximum expression, which appeared independent of multiplicities of infection greater than 1, occurring at 48 h. After 48 h, levels of cell surface and secreted p97 fell whereas p97 retained within the cell increased, which possibly reflected the lytic nature of the expression system. The successful expression of GPI‐anchored human p97 by the baculovirus/insect cell system not only provides a source of p97 for further research but also is the basis of an alternative method for the commercial production of GPI‐anchored proteins. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 41–53, 1997.

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A novel iron uptake mechanism mediated by GPI-anchored human p97.

Cited by 97 publications

References 58 publications

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

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

Multivalent Metal-Induced Iron Acquisition from Transferrin and Lactoferrin by Myeloid Cells

Expression of cell surface GPI-anchored human p97 in baculovirus-infected insect cells

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