Correlation of Transferrin Receptor Expression With Histological Class and Outcome in Non-Hodgkin Lymphoma

Habeshaw, J. A.; Lister, T. A.; Stansfeld, A. G.; Greaves, Melvyn F.

doi:10.1016/s0140-6736(83)92191-8

Cited by 175 publications

(79 citation statements)

References 17 publications

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“…In the U.S., more than 100,000 new cases of blood-related cancers are diagnosed every year (see The Leukemia and Lymphoma Society's web page, www.leukemia.org). Leukemia and lymphoma cells, which are of hematopoietic origin, overexpress the TfR compared with normal tissues (6,9,14,15) and may be especially sensitive to the cytotoxic effect of anti-TfR. Furthermore, it is possible that tumor-specific cytotoxicity can be enhanced by using anti-human TfR IgG3-Av to deliver biotinylated cytotoxic molecules.…”

Section: Discussionmentioning

confidence: 99%

“…In normal tissues, constitutive expression of the TfR is limited to the liver, epidermis, intestinal epithelium, vascular endothelium of brain capillary, and certain populations of blood cells in the bone marrow (5)(6)(7)(8)(9). In contrast, high levels of TfR expression have been identified on many tumors (5,(10)(11)(12)(13)(14)(15). In fact, studies have shown that the TfR is expressed more abundantly in malignant tissues than their normal counterparts (5,13,16,17).…”

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An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells

Cruz

Sorour

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

120

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We have developed an antibody fusion protein (anti-rat TfR IgG3-Av) with the ability to deliver different molecules into cancer cells. It consists of avidin genetically fused to the CH3 region of a human IgG3 specific for the rat transferrin receptor. It forms strong, noncovalent interactions with biotinylated molecules such as glucose oxidase and ␤-galactosidase, and delivers them into the rat myeloma cell line Y3-Ag1.2.3 through receptor-mediated endocytosis. Importantly, the ␤-galactosidase retains activity after internalization. Furthermore, we have unexpectedly discovered that anti-rat TfR IgG3-Av, but not a recombinant anti-rat TfR IgG3 or a nonspecific IgG3-Av, possesses proapoptotic activities against Y3-Ag1.2.3 and the rat T cell lymphoma cell line C58 (NT) D.1.G.OVAR.1. These activities were not observed in two rat cell lines of nonhematopoietic lineage (bladder carcinoma BC47 and gliosarcoma9L).Anti-humanTfRIgG3-Avalsodemonstratedproapoptotic activity against the human erythroleukemia cell line K562. Studies showed that anti-rat TfR IgG3-Av exists as a dimer, suggesting that cross-linking of the surface transferrin receptor may be responsible for the cytotoxic activity. These findings demonstrate that it is possible to transform an antibody specific for a growth factor receptor that does not exhibit inhibitory activity into a drug with significant intrinsic cytotoxic activity against selected cells by fusing it with avidin. The antitumor activity may be enhanced by delivering biotinylated therapeutics into cancer cells. Further development of this technology may lead to effective therapeutics for in vivo eradication of hematological malignancies, and ex vivo purging of cancer cells in autologous transplantation.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells

Cruz

Sorour

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

120

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“…Recently, methods have been used to determine the proliferation rate in NHL, based on the measurement of transferrin receptor (TR) status (Habeshaw et al, 1983) thymidine uptake (Kvaloy et al, 1985; Costa et al, 1981a) or the determination of cells in S-phase by flow cytometry (Roos et al, 1985). The proliferating fraction in NHL may give additional valuable information relevant to therapy and prognosis.…”

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confidence: 99%

A comparison of three methods for the determination of the growth fraction in non-Hodgkin's lymphoma

Schrape¹,

Jones²,

Wright³

1987

Br J Cancer

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Summary The proliferation rate of non-Hodgkin's lymphomas (NHL) was estimated by using 3 different methods. In cell suspension we determined the proportion of cells in cycle with the monoclonal antibody (Mab) Ki-67 and also in S-phase after the incorporation of bromo-deoxyruridine (BrdU) utilizing Mab antiBrdU. In low grade lymphomas 3.5 + 1.6% of the cells were in cycle and 1.2 + 0.9% in S-phase, the corresponding values for high grade lymphomas were 22.5 + 18.7% and 8.9 + 7.8% respectively.Frozen sections of NHL were reacted with an antibody to the transferrin receptor (TR) and Ki67 as markers for proliferative activity. A high number of TR positive cells was found in low grade lymphomas of all histological types, whereas Ki67 positivity correlated closely with grading. With a few exceptions, low grade lymphomas contained less than 25% Ki67 positive cells within the tumour cell population. This observation is relevant to treatment strategies for low grade NHL.Schemes for the histological classification of non-Hodgkin's lymphoma (NHL) are used to determine treatment strategies and to predict prognosis (Rosenberg et al., 1982). Recently, methods have been used to determine the proliferation rate in NHL, based on the measurement of transferrin receptor (TR) status (Habeshaw et al., 1983) thymidine uptake (Kvaloy et al., 1985; Costa et al., 1981a) or the determination of cells in S-phase by flow cytometry (Roos et al., 1985). The proliferating fraction in NHL may give additional valuable information relevant to therapy and prognosis.In this study we have compared various methods for the investigation of cells in cycle in NHL. TR status on frozen section has been compared with the monoclonal cell cycle marker Ki67 (Gerdes et al., 1984a, b) and on cell suspensions derived from biopsy material staining with Ki67 has been undertaken in parallel with the determination of S-phase using BrdU pre-incubation followed by staining with monoclonal anti-BrdU. We conclude that staining with Ki67 provides a convenient and reproducible method for cell cycle analysis which is easily included in routine monoclonal diagnostic profiles. Materials and methods SpecimensSixty fresh lymph node (LN) biopsies were obtained from the Southampton and South West Hampshire Health District. Fifty-four were subsequently diagnoses as NHL and 6 showed reactive changes only. The mean age of the patients with NHL was 60 years in both sexes, though males were twice as common as females in this group.One part of the biopsy was snap frozen in liquid nitrogen and stored at -198°C until required for immunohistologic phenotyping. A second part was fixed in formalin and processed for conventional hi'stologic examination. Histological type was assessed on this material and confirmed by immunostaining of frozen sections with an appropriate panel of monoclonal antibodies (Jones et al., 1986 The viability of mononuclear cell suspensions obtained by this method was always -90% when tested by trypan blue exclusion. The cell count was adjusted to 1 x 106 cells m...

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“…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.…”

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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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Correlation of Transferrin Receptor Expression With Histological Class and Outcome in Non-Hodgkin Lymphoma

Cited by 175 publications

References 17 publications

An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells

An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells

A comparison of three methods for the determination of the growth fraction in non-Hodgkin's lymphoma

Transferrin receptors in human cancerous tissues.

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