Purification of a cell growth factor from a human lung cancer cell line: Its relationship with ferritin

Kikyo, Nobuaki; Hagiwara, Kiyokazu; Fujisawa, Mihoko; Yazaki, Yoshio; Okabe, Tetsuro

doi:10.1002/jcp.1041610113

Cited by 18 publications

(14 citation statements)

References 19 publications

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“…This is also true in the case of human melanoma, where increased serum ferritin concentrations are associated with progressive metastatic disease (58). In addition, ferritin is produced and secreted as a cell growth factor by several cancer cells in vitro (59) and is considered responsible for some of the melanoma-induced immunosuppressive effects (60).…”

Section: Discussionmentioning

confidence: 96%

Ferritin Contributes to Melanoma Progression by Modulating Cell Growth and Sensitivity to Oxidative Stress

Baldi

Lombardi

Russo³

et al. 2005

Clinical Cancer Research

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Purpose: Employing an in vitro model system of human melanoma progression, we previously reported ferritin light chain (L-ferritin) gene overexpression in the metastatic phenotype. Here, we attempted to characterize the role of ferritin in the biology of human melanoma and in the progression of this disease. Experimental Design: Starting from the LM human metastatic melanoma cell line, we engineered cell clones in which L-ferritin gene expression was down-regulated by the stable expression of a specific antisense construct. These cells were then assayed for their growth capabilities, chemoinvasive properties, and sensitivity to oxidative stress. Additionally, ferritin protein content in primary and metastatic human melanomas was determined by immunohistochemistry. Results: Artificial L-ferritin down-regulation in the LM cells strongly inhibited proliferation and chemoinvasion in vitro and cell growth in vivo. In addition, L-ferritin down-regulated cells displayed enhanced sensitivity to oxidative stress and to apoptosis. Concurrently, immunohistochemical analysis of a human melanoma tissue array revealed that ferritin expression level in metastatic lesions was significantly higher (P < 0.0001) than in primary melanomas. Furthermore, ferritin expression was constantly up-regulated in autologous lymph node melanoma metastases when compared with the respective primary tumors in a cohort of 11patients. Conclusions: These data suggest that high ferritin expression can enhance cell growth and improve resistance to oxidative stress in metastatic melanoma cells by interfering with their cellular antioxidant system. The potential significance of these findings deserves to be validated in a clinical setting.

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Section: Discussionmentioning

confidence: 96%

Ferritin Contributes to Melanoma Progression by Modulating Cell Growth and Sensitivity to Oxidative Stress

Baldi

Lombardi

Russo³

et al. 2005

Clinical Cancer Research

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“…While the primary function of ferritin is generally considered that of an iron storage protein that regulates the bioavailability of iron, other functions, some related to iron bioavailability and others not, are emerging such as its role in cellular proliferation where L-ferritin seems to increase (Blatt & Wharton, 1992;Cozzi et al, 2004;Kakhlon et al, 2002;Kikyo et al, 1994) and H-ferritin to decrease proliferation (Cozzi et al, 2004), in erythropoiesis where the H-subunit/L-subunit ratio is important in supporting iron supply for haemoglobin synthesis or storage of excess iron (Hodgetts et al, 1986) and its regulatory role in the immune system where H-subunit rich ferritins suppress certain immune responses and downregulate myelopoiesis (Broxmeyer, 1984;Torti & Torti, 1994). Of interest is the fact that the suggested opposing effects of H-and L-ferritin would appear to be mediated through different mechanisms with the suppressive function of H-ferritin brought about by its effect on bioavailable iron with that of L-ferritin being independent of bioavailable iron (Cozzi et al, 2004).…”

Section: +mentioning

confidence: 99%

Ferritin and ferritin isoforms I: Structure–function relationships, synthesis, degradation and secretion

Koorts

Viljoen

2007

Archives of Physiology and Biochemistry

133

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Ferritin is the intracellular protein responsible for the sequestration, storage and release of iron. Ferritin can accumulate up to 4500 iron atoms as a ferrihydrite mineral in a protein shell and releases these iron atoms when there is an increase in the cell's need for bioavailable iron. The ferritin protein shell consists of 24 protein subunits of two types, the H-subunit and the L-subunit. These ferritin subunits perform different functions in the mineralization process of iron. The ferritin protein shell can exist as various combinations of these two subunit types, giving rise to heteropolymers or isoferritins. Isoferritins are functionally distinct and characteristic populations of isoferritins are found depending on the type of cell, the proliferation status of the cell and the presence of disease. The synthesis of ferritin is regulated both transcriptionally and translationally. Translation of ferritin subunit mRNA is increased or decreased, depending on the labile iron pool and is controlled by an ironresponsive element present in the 5'-untranslated region of the ferritin subunit mRNA. The transcription of the genes for the ferritin subunits is controlled by hormones and cytokines, which can result in a change in the pool of translatable mRNA. The levels of intracellular ferritin are determined by the balance between synthesis and degradation. Degradation of ferritin in the cytosol results in complete release of iron, while degradation in secondary lysosomes results in the formation of haemosiderin and protection against iron toxicity. The majority of ferritin is found in the cytosol. However, ferritin with slightly different properties can also be found in organelles such as nuclei and mitochondria. Most of the ferritin produced intracellularly is harnessed for the regulation of iron bioavailability; however, some of the ferritin is secreted and internalized by other cells. In addition to the regulation of iron bioavailability ferritin may contribute to the control of myelopoiesis and immunological responses.

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“…36 One must remember that a stimulatory effect on cell proliferation following L-rich ferritin addition to cultured cells has been observed before. [37][38][39] Iron incorporation is the only L-ferritin function so far established by in vitro study, 3 but this does not seem to be involved in the proproliferation activity. This suggests that L-ferritin affects some cellular pathways that remain to be identified.…”

Section: Role Of L-ferritinmentioning

confidence: 99%

Analysis of the biologic functions of H- and L-ferritins in HeLa cells by transfection with siRNAs and cDNAs: evidence for a proliferative role of L-ferritin

Cozzi¹,

Corsi

Levi

et al. 2004

Blood

113

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Purification of a cell growth factor from a human lung cancer cell line: Its relationship with ferritin

Cited by 18 publications

References 19 publications

Ferritin Contributes to Melanoma Progression by Modulating Cell Growth and Sensitivity to Oxidative Stress

Ferritin Contributes to Melanoma Progression by Modulating Cell Growth and Sensitivity to Oxidative Stress

Ferritin and ferritin isoforms I: Structure–function relationships, synthesis, degradation and secretion

Analysis of the biologic functions of H- and L-ferritins in HeLa cells by transfection with siRNAs and cDNAs: evidence for a proliferative role of L-ferritin

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