| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Pediatrics [S. D. W., R. H. L., D. W. F., V. F., B. A. K.] and Pharmacology [B. A. K.], University of Texas Southwestern Medical Center, Dallas, Texas 75235, and Cancer Research Division, Centocor, Malvern, Pennsylvania 19355 [L. R. C., V. R. Z.]
In some epithelial cells studied in vitro a membrane-bound folate receptor initiates the process for cell accumulation of 5-methyltetrahydrofolic acid. This receptor was found to be GP38, an overexpressed, glycosyl-phosphatidylinositol anchored glycoprotein, recognized by two monoclonal antibodies, designated MOv18 and MOv19. Using immunoblotting with MOv19, radioimmunoassay with MOv18 and 19, Northern blot analysis, and radioligand binding when possible, we describe the limited expression of the folate receptor in a large number of normal tissues from four autopsies. The immunoblot technique detected as little as 40 pg (
1 fmol) of receptor protein. Choroid plexus consistently had the largest amount of folate receptor. Other tissues containing substantial amounts of receptor included lung, thyroid, and kidney. The liver, intestines, muscle, cerebellum, cerebrum, and spinal cord were immunologically nonreactive. Folate receptor gene expression determined by Northern blot analysis confirmed these observations. We also show that several malignant cell lines express significantly more receptor than normal epithelial cells or fibroblasts. Specifically, malignant cells bound 
20 pmol [3H]folate/106 cells, while normal epithelial cells and fibroblasts bound 
1 pmol radioligand/106 cells. We also demonstrate that 4 of 6 brain tumors overexpress the folate receptor. These studies reveal the limited normal tissue distribution of the folate receptor, a cell surface protein which may be a useful immunological or pharmacological target for the development of selective cancer therapy.
1 Supported by NIH Grant 1RO1-CA52625 and ACS CH-228F. S. D. W. and D. F. were supported by National Cancer Institute Fellowship Training Grant 5T32-CA09640-02. B. A. K. is a Burroughs-Wellcome Scholar in Pharmacology.
2 To whom requests for reprints should be addressed, at Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235.
Received 1/10/92. Accepted 4/ 6/92.
This article has been cited by other articles:
|
|
 |
|
  E. G. Luebeck, S. H. Moolgavkar, A. Y. Liu, A. Boynton, and C. M. Ulrich Does Folic Acid Supplementation Prevent or Promote Colorectal Cancer? Results from Model-Based Predictions Cancer Epidemiol. Biomarkers Prev., June 1, 2008; 17(6): 1360 - 1367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Fisher, B. A. Siegel, S. L. Edell, N. M. Oyesiku, D. E. Morgenstern, R. A. Messmann, and R. J. Amato Exploratory Study of 99mTc-EC20 Imaging for Identifying Patients with Folate Receptor-Positive Solid Tumors J. Nucl. Med., June 1, 2008; 49(6): 899 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Iwakiri, M. Sonobe, S. Nagai, T. Hirata, H. Wada, and R. Miyahara Expression Status of Folate Receptor {alpha} Is Significantly Correlated with Prognosis in Non-Small-Cell Lung Cancers Ann. Surg. Oncol., March 1, 2008; 15(3): 889 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Muller, F. Forrer, R. Schibli, E. P. Krenning, and M. de Jong SPECT Study of Folate Receptor-Positive Malignant and Normal Tissues in Mice Using a Novel 99mTc-Radiofolate J. Nucl. Med., February 1, 2008; 49(2): 310 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. He, H. Wang, L. C. Hartmann, J.-X. Cheng, and P. S. Low In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry PNAS, July 10, 2007; 104(28): 11760 - 11765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Ashokkumar, Z. M Mohammed, N. D Vaziri, and H. M Said Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells Am. J. Clinical Nutrition, July 1, 2007; 86(1): 159 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Reddy, E. Westrick, H. K.R. Santhapuram, S. J. Howard, M. L. Miller, M. Vetzel, I. Vlahov, R. V.J. Chari, V. S. Goldmacher, and C. P. Leamon Folate Receptor-Specific Antitumor Activity of EC131, a Folate-Maytansinoid Conjugate Cancer Res., July 1, 2007; 67(13): 6376 - 6382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Reddy, R. Dorton, E. Westrick, A. Dawson, T. Smith, L.-C. Xu, M. Vetzel, P. Kleindl, I. R. Vlahov, and C. P. Leamon Preclinical Evaluation of EC145, a Folate-Vinca Alkaloid Conjugate Cancer Res., May 1, 2007; 67(9): 4434 - 4442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yang, E. A. Kolb, J. Qin, A. Chou, R. Sowers, B. Hoang, J. H. Healey, A. G. Huvos, P. A. Meyers, and R. Gorlick The Folate Receptor {alpha} Is Frequently Overexpressed in Osteosarcoma Samples and Plays a Role in the Uptake of the Physiologic Substrate 5-Methyltetrahydrofolate Clin. Cancer Res., May 1, 2007; 13(9): 2557 - 2567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sunamoto, K. Ushio, and D. T. Lai Folate-Modified Cholesterol-Bearing Pullulan, a New Cancer-Targeted Nanoparticle Drug Carrier: Synthesis and Applications Journal of Bioactive and Compatible Polymers, November 1, 2006; 21(6): 603 - 617. [Abstract] [PDF]
|
|
|
|
|
|
K. Hasegawa, T. Nakamura, M. Harvey, Y. Ikeda, A. Oberg, M. Figini, S. Canevari, L. C. Hartmann, and K.-W. Peng The Use of a Tropism-Modified Measles Virus in Folate Receptor-Targeted Virotherapy of Ovarian Cancer. Clin. Cancer Res., October 15, 2006; 12(20): 6170 - 6178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Knutson, C. J. Krco, C. L. Erskine, K. Goodman, L. E. Kelemen, P. J. Wettstein, P. S. Low, L. C. Hartmann, and K. R. Kalli T-Cell Immunity to the Folate Receptor Alpha Is Prevalent in Women With Breast or Ovarian Cancer J. Clin. Oncol., September 10, 2006; 24(26): 4254 - 4261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bettio, M. Honer, C. Muller, M. Bruhlmeier, U. Muller, R. Schibli, V. Groehn, A. P. Schubiger, and S. M. Ametamey Synthesis and Preclinical Evaluation of a Folic Acid Derivative Labeled with 18F for PET Imaging of Folate Receptor-Positive Tumors J. Nucl. Med., July 1, 2006; 47(7): 1153 - 1160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. McGuire, W. H. Haile, and C.-C. Yeh 5-amino-4-imidazolecarboxamide riboside potentiates both transport of reduced folates and antifolates by the human reduced folate carrier and their subsequent metabolism. Cancer Res., April 1, 2006; 66(7): 3836 - 3844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Kukowska-Latallo, K. A. Candido, Z. Cao, S. S. Nigavekar, I. J. Majoros, T. P. Thomas, L. P. Balogh, M. K. Khan, and J. R. Baker Jr. Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer Cancer Res., June 15, 2005; 65(12): 5317 - 5324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W.L. Ma, R. H. Finnell, L. A. Davidson, E. S. Callaway, O. Spiegelstein, J. A. Piedrahita, J. M. Salbaum, C. Kappen, B. R. Weeks, J. James, et al. Folate Transport Gene Inactivation in Mice Increases Sensitivity to Colon Carcinogenesis Cancer Res., February 1, 2005; 65(3): 887 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Jhaveri, A. S. Rait, K.-N. Chung, J. B. Trepel, and E. H. Chang Antisense oligonucleotides targeted to the human {alpha} folate receptor inhibit breast cancer cell growth and sensitize the cells to doxorubicin treatment Mol. Cancer Ther., December 1, 2004; 3(12): 1505 - 1512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chattopadhyay, Y. Wang, R. Zhao, and I. D. Goldman Lack of Impact of the Loss of Constitutive Folate Receptor {alpha} Expression, Achieved by RNA Interference, on the Activity of the New Generation Antifolate Pemetrexed in HeLa Cells Clin. Cancer Res., December 1, 2004; 10(23): 7986 - 7993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Toth, H. Djeha, B. Ying, A. E. Tollefson, M. Kuppuswamy, K. Doronin, P. Krajcsi, K. Lipinski, C. J. Wrighton, and W. S. M. Wold An Oncolytic Adenovirus Vector Combining Enhanced Cell-to-Cell Spreading, Mediated by the ADP Cytolytic Protein, with Selective Replication in Cancer Cells with Deregulated Wnt Signaling Cancer Res., May 15, 2004; 64(10): 3638 - 3644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Reddy, L.-C. Xu, N. Parker, M. Vetzel, and C. P. Leamon Preclinical Evaluation of 99mTc-EC20 for Imaging Folate Receptor-Positive Tumors J. Nucl. Med., May 1, 2004; 45(5): 857 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Takada, K. Fujioka, M. Tsuiji, A. Morikawa, N. Higashi, H. Ebihara, D. Kobasa, H. Feldmann, T. Irimura, and Y. Kawaoka Human Macrophage C-Type Lectin Specific for Galactose and N-Acetylgalactosamine Promotes Filovirus Entry J. Virol., March 15, 2004; 78(6): 2943 - 2947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Barzon, M. Boscaro, and G. Palu Endocrine Aspects of Cancer Gene Therapy Endocr. Rev., February 1, 2004; 25(1): 1 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Doucette and V. L. Stevens Point Mutations Alter the Cellular Distribution of the Human Folate Receptor in Cultured Chinese Hamster Ovary Cells J. Nutr., February 1, 2004; 134(2): 308 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Theti and A. L. Jackman The Role of {alpha}-Folate Receptor-Mediated Transport in the Antitumor Activity of Antifolate Drugs Clin. Cancer Res., February 1, 2004; 10(3): 1080 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gabizon, A. T. Horowitz, D. Goren, D. Tzemach, H. Shmeeda, and S. Zalipsky In Vivo Fate of Folate-Targeted Polyethylene-Glycol Liposomes in Tumor-Bearing Mice Clin. Cancer Res., December 15, 2003; 9(17): 6551 - 6559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V.T. Ramaekers, S.I. Hansen, J. Holm, T. Opladen, J. Senderek, M. Hausler, G. Heimann, B. Fowler, R. Maiwald, and N. Blau Reduced folate transport to the CNS in female Rett patients Neurology, August 26, 2003; 61(4): 506 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Theti, V. Bavetsias, L. A. Skelton, J. Titley, D. Gibbs, G. Jansen, and A. L. Jackman Selective Delivery of CB300638, a Cyclopenta[g]quinazoline-based Thymidylate Synthase Inhibitor into Human Tumor Cell Lines Overexpressing the {alpha}-Isoform of the Folate Receptor Cancer Res., July 1, 2003; 63(13): 3612 - 3618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. M. Kelley, B. G. Rowan, and M. Ratnam Modulation of the Folate Receptor {alpha} Gene by the Estrogen Receptor: Mechanism and Implications in Tumor Targeting Cancer Res., June 1, 2003; 63(11): 2820 - 2828. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hao, H. Qi, and M. Ratnam Modulation of the folate receptor type {beta} gene by coordinate actions of retinoic acid receptors at activator Sp1/ets and repressor AP-1 sites Blood, June 1, 2003; 101(11): 4551 - 4560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Siegel, F. Dehdashti, D. G. Mutch, D. A. Podoloff, R. Wendt, G. P. Sutton, R. W. Burt, P. R. Ellis, C. J. Mathias, M. A. Green, et al. Evaluation of 111In-DTPA-Folate as a Receptor-Targeted Diagnostic Agent for Ovarian Cancer: Initial Clinical Results J. Nucl. Med., May 1, 2003; 44(5): 700 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zheng, K. Kelley, H. Elnakat, W. Yan, T. Dorn, and M. Ratnam mRNA Instability in the Nucleus Due to a Novel Open Reading Frame Element Is a Major Determinant of the Narrow Tissue Specificity of Folate Receptor {alpha} Mol. Cell. Biol., March 15, 2003; 23(6): 2202 - 2212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tomassetti, F. Mangiarotti, M. Mazzi, S. Sforzini, S. Miotti, E. Galmozzi, P. C. Elwood, and S. Canevari The Variant Hepatocyte Nuclear Factor 1 Activates the P1 Promoter of the Human {alpha}-Folate Receptor Gene in Ovarian Carcinoma Cancer Res., February 1, 2003; 63(3): 696 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Q. Pan, X. Zheng, G. Shi, H. Wang, M. Ratnam, and R. J. Lee Strategy for the treatment of acute myelogenous leukemia based on folate receptor beta -targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid Blood, June 28, 2002; 100(2): 594 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Alvarez, F. Lasala, J. Carrillo, O. Muniz, A. L. Corbi, and R. Delgado C-Type Lectins DC-SIGN and L-SIGN Mediate Cellular Entry by Ebola Virus in cis and in trans J. Virol., June 5, 2002; 76(13): 6841 - 6844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Doucette and V. L. Stevens Folate Receptor Function Is Regulated in Response to Different Cellular Growth Rates in Cultured Mammalian Cells J. Nutr., November 1, 2001; 131(11): 2819 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Trippett, S. Garcia, K. Manova, R. Mody, L. Cohen-Gould, W. Flintoff, and J. R. Bertino Localization of a Human Reduced Folate Carrier Protein in the Mitochondrial as Well as the Cell Membrane of Leukemia Cells Cancer Res., March 1, 2001; 61(5): 1941 - 1947. [Abstract] [Full Text]
|
|
|
|
|
|
H. Wang, X. Zheng, F. G. Behm, and M. Ratnam Differentiation-independent retinoid induction of folate receptor type beta , a potential tumor target in myeloid leukemia Blood, November 15, 2000; 96(10): 3529 - 3536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. FINNELL, J. GELINEAU-VAN WAES, G. D. BENNETT, R. C. BARBER, B. WLODARCZYK, G. M. SHAW, E. J. LAMMER, J. A. PIEDRAHITA, and J. H. EBERWINE Genetic Basis of Susceptibility to Environmentally Induced Neural Tube Defects Ann. N.Y. Acad. Sci., September 1, 2000; 919(1): 261 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Goren, A. T. Horowitz, D. Tzemach, M. Tarshish, S. Zalipsky, and A. Gabizon Nuclear Delivery of Doxorubicin via Folate-targeted Liposomes with Bypass of Multidrug-resistance Efflux Pump Clin. Cancer Res., May 1, 2000; 6(5): 1949 - 1957. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. C. Drummond, O. Meyer, K. Hong, D. B. Kirpotin, and D. Papahadjopoulos Optimizing Liposomes for Delivery of Chemotherapeutic Agents to Solid Tumors Pharmacol. Rev., December 1, 1999; 51(4): 691 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Peoples, B. W. Anderson, T. V. Lee, J. L. Murray, A. P. Kudelka, J. T. Wharton, and C. G. Ioannides Vaccine Implications of Folate Binding Protein, a Novel Cytotoxic T Lymphocyte-recognized Antigen System in Epithelial Cancers Clin. Cancer Res., December 1, 1999; 5(12): 4214 - 4223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wu, W. Gunning, and M. Ratnam Expression of Folate Receptor Type {{alpha}} in Relation to Cell Type, Malignancy, and Differentiation in Ovary, Uterus, and Cervix Cancer Epidemiol. Biomarkers Prev., September 1, 1999; 8(9): 775 - 782. [Abstract] [Full Text]
|
|
|
|
 |
|
 Z. Zhao, K. A. Koeplinger, T. Peterson, R. A. Conradi, P. S. Burton, A. Suarato, R. L. Heinrikson, and A. G. Tomasselli Mechanism, Structure-Activity Studies, and Potential Applications of Glutathione S-Transferase-Catalyzed Cleavage of Sulfonamides Drug Metab. Dispos., September 1, 1999; 27(9): 992 - 998. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Reddy, L. S. Haneline, E. F. Srour, A. C. Antony, D. W. Clapp, and P. S. Low Expression and Functional Characterization of the beta -Isoform of the Folate Receptor on CD34+ Cells Blood, June 1, 1999; 93(11): 3940 - 3948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Maziarz, H. L. Monaco, F. Shen, and M. Ratnam Complete Mapping of Divergent Amino Acids Responsible for Differential Ligand Binding of Folate Receptors alpha and beta J. Biol. Chem., April 16, 1999; 274(16): 11086 - 11091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. CURIEL Strategies to Adapt Adenoviral Vectors for Targeted Delivery Ann. N.Y. Acad. Sci., January 1, 1999; 886(1): 158 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Villanueva, E.-H. Ling, C. J. Chandler, and C. H. Halsted Membrane and tissue distribution of folate binding protein in pig Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1998; 275(5): R1503 - R1510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Morshed, D. M. Ross, and K. E. McMartin Folate Transport Proteins Mediate the Bidirectional Transport of 5-Methyltetrahydrofolate in Cultured Human Proximal Tubule Cells J. Nutr., June 1, 1997; 127(6): 1137 - 1147. [Abstract] [Full Text]
|
|
|
|
|
|
S. C. Wong, S. A. Proefke, A. Bhushan, and L. H. Matherly Isolation of Human cDNAs That Restore Methotrexate Sensitivity and Reduced Folate Carrier Activity in Methotrexate Transport-defective Chinese Hamster Ovary Cells J. Biol. Chem., July 21, 1995; 270(29): 17468 - 17475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Spinella, K. E. Brigle, E. E. Sierra, and I. D. Goldman Distinguishing between Folate Receptor-alpha-mediated Transport and Reduced Folate Carrier-mediated Transport in L1210 Leukemia Cells J. Biol. Chem., April 7, 1995; 270(14): 7842 - 7849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. R. Williams and W. F. Flintoff Isolation of a Human cDNA That Complements a Mutant Hamster Cell Defective in Methotrexate Uptake J. Biol. Chem., February 17, 1995; 270(7): 2987 - 2992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zhao, R. G. Russell, Y. Wang, L. Liu, F. Gao, B. Kneitz, W. Edelmann, and I. D. Goldman Rescue of Embryonic Lethality in Reduced Folate Carrier-deficient Mice by Maternal Folic Acid Supplementation Reveals Early Neonatal Failure of Hematopoietic Organs J. Biol. Chem., March 23, 2001; 276(13): 10224 - 10228. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
