Transferrin is also associated with the innate immune system. It is found in the mucosa and binds iron, thus creating an environment low in free iron that impedes bacterial survival in a process called iron withholding. The level of transferrin decreases in inflammation.["
Many conditions including infection and malignancy can depress transferrin levels. The transferrin is abnormally high in iron deficiency anemia.
David Goodsell
" several molecules called lactoferrin and ovotransferrin are similar to transferrin. These molecules, found in milk and egg whites respectively, also have strong binding sites for iron. However, their main function is not delivery. Instead, they serve to protect cells from bacteria. Since they mop up any free iron ions, they starve bacteria of a vital resource, slowing the growth of an infection."
Ponka et al.
" Cellular iron uptake and storage are coordinately regulated through a feedback control mechanism mediated at the post-transcriptional level by cytoplasmic factors know as iron-regulatory proteins 1 and 2. These proteins "sense" levels of iron in the transit pool and, when iron in this pool is scarce, they bind to stem-loop structures known as iron-responsive elements on the 5' untranslated region of the ferritin mRNA and 3' untranslated region of the transferrin mRNA. Such a binding inhibits translation of ferritin mRNA and stabilizes the mRNA for transferrin receptors. The opposite scenario develops when iron in the transit pool is plentiful. This remarkable regulatory mechanism prevents the expansion of a catalytically active intracellular iron pool, while maintaining sufficient concentrations of the metal for metabolic needs.
"
using transferrin and iron chelators are extremely complex. Improperly
managed iron storage and delivery in cell culture systems is a major
contributor to oxidative stress and protein damage. For a more complete
discussion of transferrin and iron chelators as a cell culture
components go to Sigma's Media Expert.
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Primary Functions of Transferrin in Cell Culture Systems:
- Transferrins facilitate extracellular iron storage, and transport.
- Transferrins are important extracellular antioxidants. They bind iron so tightly under physiological conditions that virtually no free iron exists to catalyze the production of free radicals.
- The delivery of iron to cells by transferrins is a receptor-mediated and controlled process. Cells regulate the amount of iron they receive from the extracellular environment by varying transferrin receptor expression
- Ceruloplasmin mediated oxidation of iron is accompanied by the conversion of di-oxygen into water. Ceruloplasmin is the only circulating molecule that provides controlled and rapid oxidation of ferrous to ferric iron.
" We previously found that transferrin (Tf) differentially stimulated the growth of highly metastatic variant lines of murine melanoma and that these highly metastatic cells also had greater numbers of Tf receptors on their cell surfaces. In the present study we found that highly metastatic rat mammary adenocarcinoma cell lines also responded differentially to Tf in proliferation assays,"
Breast Cancer Res Treat. 1999 Aug;56(3):203-17.
Transferrin receptor overexpression enhances transferrin responsiveness and the metastatic growth of a rat mammary adenocarcinoma cell line.
Source
Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.Abstract
"We previously found that breast cancer cell transferrin receptor expression and proliferative response to transferrin often correlated with metastatic capability.We previously found that transferrin (Tf) differentially stimulated the growth of highly metastatic variant lines of murine melanoma and that these highly metastatic cells also had greater numbers of Tf receptors on their cell surfaces. In the present study we found that highly metastatic rat mammary adenocarcinoma cell lines also responded differentially to Tf in proliferation assays,
" Nochoson et al.
The growth of brain-metastasizing melanoma cells appears to be stimulated by other paracrine growth factors, such as paracrine transferrin. Melanoma cells metastatic to brain express higher numbers of transferrin receptors and respond and proliferate at lower concentrations of transferrin than do melanoma cells metastatic to other sites or poorly metastatic melanoma cells. The results suggest that degradation and invasion of brain basement membrane and responses to paracrine neurotrophins and paracrine transferrins are important properties in brain metastasis of murine and human malignant melanoma cells."
" A major organ-derived (paracrine) growth factor has been isolated that differentially stimulates the growth of cells metastatic to the brain. Characterization of this mitogen demonstrated that it is a transferrin-like glycoprotein; cells that are metastatic to brain express greater numbers of transferrin receptors on their surfaces than cells that are poorly metastatic or metastatic to other sites. Transferrin-like factors are expressed in fetal brain and could represent the transferrin-like factors that stimulate growth of brain-"metastatic melanoma and breast cancer cells. These and other factors are probably important in determining whether metastatic cells can successfully invade, colonize, and grow in the CNS."
Reversal by Transferrin of Growth-Inhibitory Effect of Suramin on Hormone-Refractory Human Prostate Cancer Cells
+ Author Affiliations
- *Correspondence to: Waren D. W. Heston, Ph.D., Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 334, New York, NY 10021.
Antisense oligonucleotide targeted to the transferrin receptor gene suppresses tumor growth and lung metastases in 4T1 mammary adenocarcinoma mouse model
X. Jiang, A. Israyeeyan, E. Boykin, L. Lomax, J. F. Head and R. L. Elliott Mastology Research Institute, Baton Rouge, LA; School of Veterinary Medical, LSU, Baton Rouge, LA10616
Iron is required for the activity of ribonucleotide reductase and synthesis of DNA. Cellular surface transferrin receptors (TfR) are the principal transport protein for iron into cells. It has been reported that inhibition of TfR gene expression leads to the suppression of tumor cell growth in cell culture. In the present study, an antisense oligonucleotide targeted to the transferrin receptor gene was used to treat 4T1 mammary adenocarinoma in cell culture and a mouse model. The cytotoxicity of a 24-mer TfR antisense oligonucleotide was determined by 3[H]-thymidine incorporation in vitro. The sense and random sequence
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