Expression and functional characterization of the β-isoform of the folate receptor on CD34+ cells

被引:85
作者
Reddy, JA
Haneline, LS
Srour, EF
Antony, AC
Clapp, DW
Low, PS
机构
[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA
[2] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA
[3] Indiana Univ, Sch Med, Div Hematol Oncol, Indianapolis, IN USA
[4] Indiana Univ, Sch Med, Dept Immunol Microbiol, Indianapolis, IN USA
[5] Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN USA
[6] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA
关键词
D O I
10.1182/blood.V93.11.3940.411k09_3940_3948
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We have investigated the expression and functional competence of folate receptor (FR) isoforms on human hematopoietic cells. Using immunofluorescence and reverse transcriptase-polymerase chain reaction (RT-PCR) methodology, we find that a substantial fraction of low-density mononuclear and CD34(+) cells express both the beta and gamma isoforms of FR. The alpha isoform of FR (the form most commonly found on cancer cells) was surprisingly absent from all hematopoietic cells examined, Compared with KB cells (a human cell line known for its elevated expression of FR-alpha), the abundance of FR-beta on CD34(+) cell surfaces was relatively low (approximate to 8% of KB cell levels). Because many antifolates and folic acid-linked chemotherapeutic agents enter malignant cells at least partially via FR endocytosis, it was important to evaluate the ability of FR on CD34(+) cells to bind folic acid (FA), Based on three FR binding assays, freshly isolated CD34(+) cells were found to display no affinity for FA. Thus, regardless of whether steps were taken to remove endogenous folates before receptor binding assays, FR on primitive hematopoietic cells failed to bind H-3-FA, fluorescein isothiocyanate (FITC)-linked FA, or FA-derivatized liposomes. In contrast, analogous studies on KB cells showed high levels of receptor binding for all three FR probes. These studies show that although multipotent hematopoietic progenitor cells express FR, the receptor does not transport significant amounts of FA, Consequently, antifolates and FA-linked chemotherapeutic agents that can be engineered to enter malignant cells exclusively through the FR should not harm progenitor/stem cell function, (C) 1999 by The American Society of Hematology.
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页码:3940 / 3948
页数:9
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