Demonstration of an epitope of the transferrin receptor in human cervical epithelium--a potentially useful cell marker.

Lloyd, J M; O'Dowd, T.; Driver, Marie; Tee, D E

doi:10.1136/jcp.37.2.131

Cited by 46 publications

(17 citation statements)

References 14 publications

(1 reference statement)

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“…2A). The increased level of transferrin receptor in vitro correlates with in vivo data showing increased transferrin receptors in high-grade cervical lesions and cancers as measured by immunohistochemistry (14)(15)(16). Thus, the increase in transferrin receptors is not an artifact of in vitro culturing of the cells.…”

Section: Resultssupporting

confidence: 61%

“…In a subsequent study, the cervical cancer cell line HeLa was also shown to be sensitive to DHA although a mechanism for cell death was not elucidated (8). We speculated that both cervical cancer and immortalized cell lines, which are sensitized to apoptotic cell death by the expression of the E6 and E7 oncogenes (9-13) and overexpress the transferrin receptor (14)(15)(16), might be killed by these antimalarial compounds.…”

Section: Introductionmentioning

confidence: 99%

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Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

et al. 2005

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Nearly all cervical cancers are etiologically attributable to human papillomavirus (HPV) infection and pharmaceutical treatments targeting HPV-infected cells would be of great medical benefit. Because many neoplastic cells (including cervical cancer cells) overexpress the transferrin receptor to increase their iron uptake, we hypothesized that irondependent, antimalarial drugs such as artemisinin might prove useful in treating HPV-infected or transformed cells. We tested three different artemisinin compounds and found that dihydroartemisinin (DHA) and artesunate displayed strong cytotoxic effects on HPV-immortalized and transformed cervical cells in vitro with little effect on normal cervical epithelial cells. DHA-induced cell death involved activation of the mitochondrial caspase pathway with resultant apoptosis. Apoptosis was p53 independent and was not the consequence of drug-induced reductions in viral oncogene expression. Due to its selective cytotoxicity, hydrophobicity, and known ability to penetrate epithelial surfaces, we postulated that DHA might be useful for the topical treatment of mucosal papillomavirus lesions. To test this hypothesis, we applied DHA to the oral mucosa of dogs that had been challenged with the canine oral papillomavirus. Although applied only intermittently, DHA strongly inhibited viral-induced tumor formation. Interestingly, the DHA-treated, tumor-negative dogs developed antibodies against the viral L1 capsid protein, suggesting that DHA had inhibited tumor growth but not early rounds of papillomavirus replication. These findings indicate that DHA and other artemisinin derivatives may be useful for the topical treatment of epithelial papillomavirus lesions, including those that have progressed to the neoplastic state. (Cancer Res 2005; 65(23): 10854-61)

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Section: Resultssupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

et al. 2005

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“…This study shows that the content of receptors specific for transferrin in various cancerous tissues including the lung, stomach, colon and breast is substantially greater than that of normal conterpart. Lloyd et al (1984) have described that only a small amount of Tf • R was observed either in normal of dysplastic epithelia of uterine cervical biopsy specimens by immunohistochemical study. We have found that the amount of Tf.…”

Section: Discussionmentioning

confidence: 99%

Transferrin receptors in human cancerous tissues.

Niitsu

Kohgo

Nishisato

et al. 1987

Tohoku J. Exp. Med.

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The clinical significance of radioreceptor assay for transferrin receptors of human cancerous tissues was evaluated. Fresh surgical specimens from various carcinoma tissues were solubilized with 1% Triton X-100 and the extracts were mixed with '25I-labelled diferric transferrin. The free transferrin and the receptor-bound transferrin were separated by 15% polyethylene glycol precipitation. The % specific transferrin binding to gastric, colonic, lung and mammary carcinoma tissues ranged between 3.9 and 13.9%, whereas those for normal stomach and colon were less than 2%. The concentrations of transferrin receptors in these cancerous tissues ranged between 3.7 and 28.3 pmole/g tissues. It was concluded that the amounts of transferrin receptors were significantly increased in all of the tumor tissue extracts examind and may thereby provide a useful marker for the diagnosis of malignancies. transferrin receptor ; transferrin ; radioreceptor assay ; cell proliferationThe first event in cellular iron uptake is the binding of differric transferrin to its receptors (Aisen and Listowsky 1980). In addition to erythroid cells (Jandl and Katz 1963), transferrin receptors (Tf • R) have been found in established cell lines in vitro (Hamilton et al. 1979;Trowbridge and Omary 1981). Recently, Shindelman et al. (1981) and Habeshow and Lister (1983) have reported the presence of Tf.• R in the tissue of breast cancer and malignant lymphoma, respectively. Furthermore, it has become apparent that the Tf.• R are expressed in much greater amounts on malignant cells than on non-malignant cells, although a quantitative study is lacking. These findings have generated a considerable interest on Tf.• R which appear to be a marker of malignant transformation.In the present paper, we investigated Tf.• R in surgical specimens obtained from a variety of different types of human malignancy. The results of our study indicate that Tf•R may be useful as a marker of cell proliferation.

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“…25,55 Because of the pivotal role of TfR in Fe uptake, the TfR is more abundantly expressed in rapidly dividing cells than quiescent cells, 56,57 and high levels of TfR expression have been identified on many tumors. [58][59][60] In fact, studies have shown that expression of TfR is more abundant in breast cancer tissue than in normal tissue. 60,61 Given the facts that estrogen and Fe exert their biological effects through their receptors, 62,63 it is important to know whether E2 affects TfR in cells with different ER and PR status.…”

Section: Discussionmentioning

confidence: 99%

Roles of hormone replacement therapy and iron in proliferation of breast epithelial cells with different estrogen and progesterone receptor status

et al. 2008

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Estrogen and iron play critical roles in a female body development and were investigated in the present study in relation to in vitro cell proliferation. Prempro™, a hormone replacement therapy drug, and 17β-estradiol (E2) were shown to increase cell proliferations in estrogen receptor positive (ER + ) cells independent of progesterone receptor (PR) status. For example, increased cell proliferation was observed in ER + /PR + human breast cancer MCF-7, its matching non-cancerous human breast epithelial MCF-12A, and ER + /PR + murine mammary cancer MXT + cells, but not in ER − /PR − MDA-MB-231, its matching non-cancerous MCF-10A, and MXT − (ER − /PR + ) cells. By mimicking post-menopausal conditions of high estrogen in local breast tissue and increased iron levels due to cessation of menstrual periods, E2 and iron were shown to exert synergistic effects on proliferation of MCF-7 cells and significantly increased Ki67 and proliferating cell nuclear antigen. Western blotting of E2-treated ER + but not ER − cells showed that E2 also increased transferrin receptor (TfR). Further studies are needed to assess the mitogenic effects of iron and estrogen in normal post-menopausal breast.

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Demonstration of an epitope of the transferrin receptor in human cervical epithelium--a potentially useful cell marker.

Cited by 46 publications

References 14 publications

Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells In vitro and In vivo

Transferrin receptors in human cancerous tissues.

Roles of hormone replacement therapy and iron in proliferation of breast epithelial cells with different estrogen and progesterone receptor status

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