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Iron: a target for the management of Kaposi's sarcoma?

Simonart T - BMC Cancer (2004)

Bottom Line: Based on the apoptotic and antiproliferative effect of iron chelation on KS cells, it is suggested that iron withdrawal strategies could be developed for the management of KS.Studies using potent iron chelators in suitable KS animal models are critical to evaluate whether iron deprivation may be a useful anti-KS strategy.It is suggested that iron may be one of non-viral co-factors involved of KS pathogenesis and that iron withdrawal strategies might interfere with tumour growth in patients with KS.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Dermatology, Erasme University Hospital, Route de Lennik 808, B-1070 Brussels, Belgium. tsimonar@ulb.ac.be

ABSTRACT

Background: Kaposi's sarcoma (KS) is a mesenchymal tumour associated with human herpesvirus-8 infection. However, the incidence of human herpesvirus-8 infection is far higher than the prevalence of KS, suggesting that viral infection per se is not sufficient for the development of malignancy and that one or more additional cofactors are required.

Discussion: Epidemiological data suggest that iron may be one of the cofactors involved in the pathogenesis of KS. Iron is a well-known carcinogen and may favour KS growth through several pathways. Based on the apoptotic and antiproliferative effect of iron chelation on KS cells, it is suggested that iron withdrawal strategies could be developed for the management of KS. Studies using potent iron chelators in suitable KS animal models are critical to evaluate whether iron deprivation may be a useful anti-KS strategy.

Summary: It is suggested that iron may be one of non-viral co-factors involved of KS pathogenesis and that iron withdrawal strategies might interfere with tumour growth in patients with KS.

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'Plaque-stage' KS showing the presence of numerous haemosiderin-laden macrophages.
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Figure 3: 'Plaque-stage' KS showing the presence of numerous haemosiderin-laden macrophages.

Mentions: The pathogenic role of iron in cancer development and/or progression is not fully understood. Several carcinogenic pathways have schematically been described: (a) iron is an essential element for dividing cells, because it is incorporated in numerous enzymes that play a role in DNA replication and cellular metabolism. More particularly, iron can directly promote the growth of some cancer cells [30], probably through its role in the activation of ribonucleotide reductase, a key-enzyme in DNA synthesis, responsible for the reduction of ribonucleotides to deoxyribonucleotides [31]; (b) iron may promote the formation of mutagenic hydroxyl radicals [23]; (c) iron excess diminishes host defences through inhibition of the activity of CD4 lymphocytes and through the suppression of the tumoricidal action of macrophages [23]; (d) iron can enhance host cell production of viral nucleic acids [32] which may be involved in the development of some human cancers. Other data support more specifically a direct role of iron in the pathogenesis of KS: 1) the addition of iron salts to KS-derived cells can stimulate their growth [33]; 2) iron can induce the expression of anti-apoptotic signals in human dermal microvascular endothelial cells [34], which may alter the homeostasis of microvessels and promote neo-angiogenesis. Interestingly, one of the histological hallmark of KS is the presence of ferritin granules and the presence of haemosiderin-laden macrophages (figure 3). Even at the early 'patch-stage' of KS development, red blood cell extravasation and the presence of siderophages are encountered, providing a possible continuous source of iron for endothelial and KS cells.


Iron: a target for the management of Kaposi's sarcoma?

Simonart T - BMC Cancer (2004)

'Plaque-stage' KS showing the presence of numerous haemosiderin-laden macrophages.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC317471&req=5

Figure 3: 'Plaque-stage' KS showing the presence of numerous haemosiderin-laden macrophages.
Mentions: The pathogenic role of iron in cancer development and/or progression is not fully understood. Several carcinogenic pathways have schematically been described: (a) iron is an essential element for dividing cells, because it is incorporated in numerous enzymes that play a role in DNA replication and cellular metabolism. More particularly, iron can directly promote the growth of some cancer cells [30], probably through its role in the activation of ribonucleotide reductase, a key-enzyme in DNA synthesis, responsible for the reduction of ribonucleotides to deoxyribonucleotides [31]; (b) iron may promote the formation of mutagenic hydroxyl radicals [23]; (c) iron excess diminishes host defences through inhibition of the activity of CD4 lymphocytes and through the suppression of the tumoricidal action of macrophages [23]; (d) iron can enhance host cell production of viral nucleic acids [32] which may be involved in the development of some human cancers. Other data support more specifically a direct role of iron in the pathogenesis of KS: 1) the addition of iron salts to KS-derived cells can stimulate their growth [33]; 2) iron can induce the expression of anti-apoptotic signals in human dermal microvascular endothelial cells [34], which may alter the homeostasis of microvessels and promote neo-angiogenesis. Interestingly, one of the histological hallmark of KS is the presence of ferritin granules and the presence of haemosiderin-laden macrophages (figure 3). Even at the early 'patch-stage' of KS development, red blood cell extravasation and the presence of siderophages are encountered, providing a possible continuous source of iron for endothelial and KS cells.

Bottom Line: Based on the apoptotic and antiproliferative effect of iron chelation on KS cells, it is suggested that iron withdrawal strategies could be developed for the management of KS.Studies using potent iron chelators in suitable KS animal models are critical to evaluate whether iron deprivation may be a useful anti-KS strategy.It is suggested that iron may be one of non-viral co-factors involved of KS pathogenesis and that iron withdrawal strategies might interfere with tumour growth in patients with KS.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Dermatology, Erasme University Hospital, Route de Lennik 808, B-1070 Brussels, Belgium. tsimonar@ulb.ac.be

ABSTRACT

Background: Kaposi's sarcoma (KS) is a mesenchymal tumour associated with human herpesvirus-8 infection. However, the incidence of human herpesvirus-8 infection is far higher than the prevalence of KS, suggesting that viral infection per se is not sufficient for the development of malignancy and that one or more additional cofactors are required.

Discussion: Epidemiological data suggest that iron may be one of the cofactors involved in the pathogenesis of KS. Iron is a well-known carcinogen and may favour KS growth through several pathways. Based on the apoptotic and antiproliferative effect of iron chelation on KS cells, it is suggested that iron withdrawal strategies could be developed for the management of KS. Studies using potent iron chelators in suitable KS animal models are critical to evaluate whether iron deprivation may be a useful anti-KS strategy.

Summary: It is suggested that iron may be one of non-viral co-factors involved of KS pathogenesis and that iron withdrawal strategies might interfere with tumour growth in patients with KS.

Show MeSH
Related in: MedlinePlus