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Folate receptors as potential therapeutic targets in choroid plexus tumors of SV40 transgenic mice
T A Patrick1, D M Kranz, T A van Dyke
1Neuroscience Program, University of Illinois, Urbana 61801, USA.
Abstract:
A high affinity folate receptor is expressed in some human cancers, including choroid plexus tumors and ependymomas, and has been suggested as a target for therapeutics. In this report, the expression of folate receptors in an SV40 large T antigen transgenic mouse (SV11) was investigated. SV11 mice develop choroid plexus tumors, a property that may be related to the observation that SV40 has been isolated from human choroid plexus tumors and ependymomas. We report that SV11 choroid plexus tumors contain a high affinity folate receptor (KD of 1 nM), detectable by 125I-folate autoradiography and immunohistochemistry. Western blot analysis indicated an apparent molecular weight of 38 kDa. RT-PCR revealed the presence of transcripts for both alpha and beta isoforms of the folate receptor. Brain parenchyma has undetectable folate receptor, but normal choroid plexus has substantial levels (as does human choroid plexus). The folate receptors of the tumor are accessible from the bloodstream whereas those of the normal choroid plexus are not. Thus SV11 transgenic mice should be useful for evaluating therapeutic targeting of high affinity folate receptors, both for efficacy of specific agents and possible side effects.
Insights
SV11 mice with choroid plexus tumors express high-affinity folate receptors. These tumor receptors are accessible from the bloodstream, making SV11 mice valuable for testing cancer therapies targeting folate receptors.
Area of Science:
- Oncology
- Molecular Biology
- Neuroscience
Background:
- High-affinity folate receptors are expressed in certain human cancers, including choroid plexus tumors and ependymomas.
- These receptors are potential therapeutic targets for cancer treatment.
Purpose of the Study:
- To investigate folate receptor expression in SV11 transgenic mice, which develop choroid plexus tumors.
- To assess the utility of SV11 mice for evaluating targeted cancer therapies.
Main Methods:
- SV11 transgenic mouse model.
- 125I-folate autoradiography and immunohistochemistry.
- Western blot analysis and RT-PCR.
Main Results:
- SV11 choroid plexus tumors exhibit high-affinity folate receptors (KD of 1 nM).
- Follicle receptor transcripts for alpha and beta isoforms were detected.
- Tumor folate receptors are accessible from the bloodstream, unlike those in normal choroid plexus.
Conclusions:
- SV11 mice serve as a relevant model for studying folate receptor expression in tumors.
- The accessibility of tumor folate receptors suggests potential for targeted drug delivery.
- SV11 mice are suitable for evaluating the efficacy and side effects of folate receptor-targeted therapeutics.