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Folate Receptor Expression In Carcinomas And Normal Tissues Determined By A Quantitative Radioligand Binding Assay.
N. Parker, M. Turk, Elaine Westrick, J. D. Lewis, P. Low, C. P. Leamon
Published 2005 · Biology, Medicine
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The folate receptor (FR) is a valuable therapeutic target that is highly expressed on a variety of cancers. The current development of folate-targeted cancer therapies has created the need for quantitating functional FRs in clinical specimens. In this article, we report on the creation of a highly sensitive radioactive binding method for quantitatively measuring FR expression in frozen tissue homogenates. Expression was positive in approximately 89% of human ovarian carcinomas but was negligible in both mucinous ovarian carcinomas and normal ovary. Expression was also significant in carcinomas of the kidney, endometrium, lung, breast, bladder, and pancreas. Normal tissues from humans and six different laboratory species were also analyzed; surprisingly, some interspecies variability in FR expression (especially in kidney, spleen, and lung tissue) was found. Interestingly, normal human lung tissue displayed high expression levels, whereas expression in normal lung of the other species was negligible. However, considering that folate-drug conjugates fail to accumulate in the lungs of patients, the consequence of this finding was not considered to be of clinical concern. Overall, this new methodology is reliable for determining functional FR expression levels in tissues, and it could possibly be a useful clinical test to determine patient candidacy for FR-targeted therapeutics.
This paper references
Folate transport proteins mediate the bidirectional transport of 5-methyltetrahydrofolate in cultured human proximal tubule cells.
K. M. Morshed (1997)
Internalization and intracellular transport of folate-binding protein in rat kidney proximal tubule.
H. Birn (1993)
Folate deficiency reduces the GPI-anchored folate-binding protein in rat renal tubules.
M. da Costa (2000)
Internalization and apical-to-basolateral transport of folate in rat kidney proximal tubule.
H. Birn (1997)
Immunohistochemical Reactivity of a Monoclonal Antibody Prepared against Human Ovarian Carcinoma on Normal and Pathological Female Genital Tissues
R. Veggian (1989)
Folic acid transport in organ-cultured mucosa of human intestine. Evidence for distinct carriers.
J. Zimmerman (1990)
Folate targeting of haptens to cancer cell surfaces mediates immunotherapy of syngeneic murine tumors
Y. Lu (2002)
Folate receptor in malignant effusions of ovarian carcinoma
J. Holm (1995)
Influence on immunoreactive folate-binding proteins of extracellular folate concentration in cultured human cells.
M. Kane (1988)
Isolation and characterization of a folate receptor from human placenta.
A. Antony (1981)
High-affinity folate binding in human choroid plexus. Characterization of radioligand binding, immunoreactivity, molecular heterogeneity and hydrophobic domain of the binding protein.
J. Holm (1991)
Delivery of folates to the cytoplasm of MA104 cells is mediated by a surface membrane receptor that recycles.
B. Kamen (1988)
Mediated uptake of folate by a high-affinity binding protein in sublines of L1210 cells adapted to nanomolar concentrations of folate
G. Henderson (2005)
Synthesis and Biological Evaluation of EC20: A New Folate-Derived, 99mTc-Based Radiopharmaceutical
C. P. Leamon (2002)
New anti‐lung‐cancer antibody cluster 12 reacts with human folate receptors present on adenocarcinoma
Wilbur A. Franklin (1994)
The isolation, characterization, and comparison of the membrane-associated and soluble folate-binding proteins from human KB cells.
P. C. Elwood (1986)
Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues.
S. Weitman (1992)
A high-affinity folate binding protein in proximal tubule cells of human kidney.
J. Holm (1992)
Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications
J. Ross (1994)
Folate-mediated targeting of therapeutic and imaging agents to cancers.
J. Reddy (1998)
Folate receptor of human mammary adenocarcinoma
J. Holm (1994)
C. P. Leamon (2004)
Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein.
L. Coney (1991)
Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein.
P. Garinchesa (1993)
Overexpression of folate binding protein in ovarian cancers
G. Toffoli (1997)
Epithelial-stromal interactions in colon cancer.
F. T. Bosman (1993)
The isolation and properties of multiple forms of folate binding protein in cultured KB cells.
C. Luhrs (1986)
Folate receptor-targeted drugs for cancer and inflammatory diseases.
P. Low (2004)
Local concentration of folate binding protein GP38 in sections of human ovarian carcinoma by in vitro quantitative autoradiography.
P. Y. Li (1996)
Expression and functional characterization of the beta-isoform of the folate receptor on CD34(+) cells.
J. Reddy (1999)
Indium-111-DTPA-folate as a potential folate-receptor-targeted radiopharmaceutical.
C. Mathias (1998)
Folate binding protein distribution in normal tissues and biological fluids from ovarian carcinoma patients as detected by the monoclonal antibodies MOv18 and MOv19.
L. Mantovani (1994)
Characterization of human ovarian carcinoma‐associated antigens defined by novel monoclonal antibodies with tumor‐restricted specificity
S. Miotti (1987)
Folate-mediated targeting: from diagnostics to drug and gene delivery.
C. P. Leamon (2001)
Folate Receptors in Malignant and Benign Tissues of Human Female Genital Tract
J. Holm (1997)
The α folate receptor is highly activated in malignant pleural mesothelioma
R. Bueno (2001)
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E. Basal (2009)
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C. H. Ng (2011)
Cellular interactions of therapeutically delivered nanoparticles
A. Kumari (2011)
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D. Pérez-Callejo (2016)
An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer.
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A. S. Canton (2019)
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R. Amato (2014)
HUMAN ENDOGENOUS RETROVIRUS K AS A NOVEL TUMOR-ASSOCIATED ANTIGEN FOR DEVELOPMENT OF AN OVARIAN CANCER VACCINE
K. Rycaj (2012)
Ligand‐Targeted Delivery of Small Interfering RNAs to Malignant Cells and Tissues
M. Thomas (2009)
Folate-conjugated boron nitride nanospheres for targeted delivery of anticancer drugs
S. Feng (2016)
Protease-activation using anti-idiotypic masks enables tumor specificity of a folate receptor 1-T cell bispecific antibody
M. Geiger (2020)
Promising potential of [177Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy—a preclinical study using a syngeneic breast cancer model
P. Guzik (2020)
Acoustic response of targeted nanodroplets post-activation using high frame rate imaging
Ge Zhang (2017)
Use of Carbonic Anhydrase IX Inhibitors for Selective Delivery of Attached Drugs to Solid Tumors
S. Gardeen (2019)
A novel tumor-targeting treatment strategy uses energy restriction via co-delivery of albendazole and nanosilver
Jianming Liang (2018)
Folate Receptor and Targeting Strategies
Bhagyashri Joshi (2019)
Principles in the design of ligand-targeted cancer therapeutics and imaging agents
M. Srinivasarao (2015)
Heterogeneity of Cancers and Its Implication for Targeted Drug Delivery
T. A. Denison (2013)
Platinum nanoparticles in nanobiomedicine.
Deborah Pedone (2017)
Co-delivery of Doxorubicin and Bmi1 siRNA by Folate Receptor Targeted Liposomes Exhibits Enhanced Anti-Tumor Effects in vitro and in vivo
Tan Yang (2014)
Expression status of folate receptor alpha is a predictor of survival in pancreatic ductal adenocarcinoma
L. Cai (2017)
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X. Xu (2017)
Folate receptor-α expression in resectable hepatic colorectal cancer metastases: patterns and significance
M. D'angelica (2011)
Improved therapeutic activity of folate-targeted liposomal doxorubicin in folate receptor-expressing tumor models
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