Characterization of multiple forms of folate-binding protein from human leukemia cells

Sadasivan, Easwara; Rothenberg, Sheldon P.; Costa, Maria Da; Brink, Larry

doi:10.1016/0304-4165(86)90253-9

Cited by 30 publications

(19 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…39 However, activated synovial macrophages in rheumatoid arthritis 36 and membranes from CML and AML spleens 22,37,38 have the ability to bind the ligand. The results of this study clearly demonstrate the inability of FR-␤ expressed on the surfaces of mature granulocytes to bind folate.…”

Section: Discussionmentioning

confidence: 99%

“…29,35,36 FR-␤ is also known to be expressed in chronic myelogenous leukemia (CML) and in AML. 22,37,38 FR-␤ from membrane preparations from CML and AML spleen samples and activated macrophage bound folic acid, 22,36 but a protein in CD34 ϩ cells immunoreactive to anti-FR antiserum did not. 39 FR-␤ expression in KG-1 AML cells and in primary AML blasts obtained from the bone marrow of AML patients may be further induced in vitro up to 20-fold by brief (1-to 5-day) treatment with all-trans retinoic acid (ATRA) in a manner independent of the induction of cell differentiation and growth inhibition.…”

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

Strategy for the treatment of acute myelogenous leukemia based on folate receptor β–targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid

Pan

Zheng

Shi

et al. 2002

Blood

177

149

View full text Add to dashboard Cite

Up-regulation of folate receptor (FR) type-␤ in acute myelogenous leukemia (AML) by all-trans retinoic acid (ATRA) and its restricted normal tissue distribution makes it a potential target for therapeutic intervention. The FR-␤ in peripheral blood granulocytes was unable to bind folate and appeared to have a variant GPI membrane anchor, evident from its insensitivity to phosphatidylinositol-specific phospholipase C but not nitrous acid. Granulocyte FR-␤ lacked mutations, and neither deglycosylation nor detergent solubilization restored folate binding. The posttranslational modification causing its nonfunctionality was evi- IntroductionAcute myelogenous leukemia (AML) is the most common type of acute leukemia in adults. Standard chemotherapy results in a 70% complete remission rate in AML patients. 1 Treatment with drugs such as anthracyclines, however, is associated with severe side effects such as myelosuppression and dose-limiting cardiotoxicity and a high incidence of relapse. 2 Relapsed disease is frequently refractory to chemotherapy and exhibits multidrug resistance (MDR). 3 A potential means of treating AML is by targeted drug delivery through liposomes. Liposomal delivery of drugs has been shown to extend their systemic circulation time, reduce dose-limiting toxicity, and overcome MDR. [4][5][6][7] Liposomal anthracyclines have reached clinical use for the treatment of Kaposi sarcoma 5 and are in clinical trial for solid tumors and leukemias. [8][9][10][11][12][13][14] Liposomal delivery has also been shown to increase anthracycline cytotoxicity in tumor cells exhibiting MDR. 6,7,[15][16][17] The efficacy of liposomal drugs can potentially be further enhanced by selective targeting to tumor cells through a cell surface molecule that is differentially expressed on tumor cells. 18,19 The folate receptor (FR) is a promising target because of its narrow tissue specificity, its overexpression in malignant tissues, and its ability to bind and internalize folic acid conjugates. Of the 3 human folate receptor isoforms, 20-22 2 (FR-␣ and FR-␤) are attached to the cell surface through a glycosyl-phosphatidylinositol (GPI) membrane anchor, 20,23 whereas the third (FR-␥) is constitutively secreted. 24 The expression of FR-␣ in normal tissues is restricted to certain epithelial cells, where it is inaccessible by the circulation. 25,26 FR-␣ is found to be amplified in many epitheliallineage human tumors, including approximately 90% of ovarian carcinomas. [26][27][28][29] A wide variety of experimental therapies, 30 including drug-loaded liposomes, 31-34 have successfully targeted FR-␣ selectively in gynecologic and other tumors. The expression of FR-␤ in normal tissues is restricted to placenta and hematopoietic cells, where it is expressed in the myelomonocytic lineage and is particularly elevated during neutrophil maturation or during monocyte or macrophage activation. 29,35,36 FR-␤ is also known to be expressed in chronic myelogenous leukemia (CML) and in AML. 22,37,38 FR-␤ from membrane preparations from CML and ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Strategy for the treatment of acute myelogenous leukemia based on folate receptor β–targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid

Pan

Zheng

Shi

et al. 2002

Blood

177

149

View full text Add to dashboard Cite

show abstract

“…The membrane FBP was purified from cells cultured in FD medium using an epoxy-activated Sepharose 6B matrix coupled to folate (24), as previously described (5,25).…”

Section: Methodsmentioning

confidence: 99%

Transfection of a glycosylated phosphatidylinositol-anchored folate-binding protein complementary DNA provides cells with the ability to survive in low folate medium.

Luhrs¹,

Raskin²,

Durbin³

et al. 1992

J. Clin. Invest.

View full text Add to dashboard Cite

KB cells express a folate-binding protein that is anchored to the plasma membrane by a glycosylated phosphatidylinositol (GPI) tail and these cells can grow in medium containing a very low folate concentration (1 nM). In contrast, mouse 3T3 cells do not express a membrane-associated folate-binding protein and cannot grow under similar low folate conditions. In these studies, 3T3 cells were transfected with a vector containing the cDNA that codes for the KB cell folate-binding protein. In contrast to the wild-type 3T3 cells, the transfected 3T3 cells express a level of folate-binding protein similar to KB cells, 1 and 1.4 ng/,ug protein, respectively. The capacity for binding 13HIfolate to the surface of transfected 3T3 cells cultured in folatedeficient medium is 7.7 pmol/ 106 cells, and this is -50% of the surface binding capacity of KB cells under similar culture conditions. Moreover, after treatment of the transfected 3T3 cells with phospholipase C specific for phosphatidylinositol, the binding of 13HI folate to the surface of these cells is reduced by 90%, indicating that, like the KB cells, the folate-binding protein is anchored to the plasma membrane by a GPI tail. Although the doubling time of wild-type 3T3 cells markedly increases after 13 d of culture in folate-deficient medium, the doubling time of both the transfected 3T3 cells and KB cells do not change. The results of these experiments indicate that the GPI-anchored folate-binding protein provides a mechanism to maintain a level of folate that permits the folate-dependent metabolic functions necessary for cell survival under low folate conditions. (J. Clin. Invest. 1992. 90:840-847.)

show abstract

“…FRβ is expressed in normal myelopoiesis and in placenta, spleen, and thymus 45,46. Functional FRβ is found in myeloid leukemia and in activated macrophages associated with inflammation and malignant tumor 20,47–52. Therefore, FRβ is potentially useful as a marker for myeloid leukemia, for chronic inflammatory diseases such as rheumatoid arthritis, and for tumor-associated macrophages 49,50,53,54.…”

Section: Folate Folate Receptors and Cancermentioning

confidence: 99%

Targeted drug delivery via folate receptors in recurrent ovarian cancer: a review

Marchetti¹,

Palaia²,

Giorgini³

et al. 2014

OTT

110

View full text Add to dashboard Cite

Ovarian cancer is the most common cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease; although chemotherapeutic advances have improved progression-free survival, conventional treatments offer limited results in terms of long-term responses and survival. Research has recently focused on targeted therapies, which represent a new, promising therapeutic approach, aimed to maximize tumor kill and minimize toxicity. Besides antiangiogenetic agents and poly (ADP-ribose) polymerase inhibitors, the folate, with its membrane-bound receptor, is currently one of the most investigated alternatives. In particular, folate receptor (FR) has been shown to be frequently overexpressed on the surface of almost all epithelial ovarian cancers, making this receptor an excellent tumor-associated antigen. There are two basic strategies to targeting FRs with therapeutic intent: the first is based on anti-FR antibody (ie, farletuzumab) and the second is based on folate–chemotherapy conjugates (ie, vintafolide/etarfolatide). Both strategies have been investigated in Phase III clinical trials. The aim of this review is to analyze the research regarding the activity of these promising anti-FR agents in patients affected by ovarian cancer, including anti-FR antibodies and folate–chemotherapy conjugates.

show abstract

Characterization of multiple forms of folate-binding protein from human leukemia cells

Cited by 30 publications

References 29 publications

Strategy for the treatment of acute myelogenous leukemia based on folate receptor β–targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid

Strategy for the treatment of acute myelogenous leukemia based on folate receptor β–targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid

Transfection of a glycosylated phosphatidylinositol-anchored folate-binding protein complementary DNA provides cells with the ability to survive in low folate medium.

Targeted drug delivery via folate receptors in recurrent ovarian cancer: a review

Contact Info

Product

Resources

About