Folate receptors as potential therapeutic targets in choroid plexus tumors of SV40 transgenic mice.
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.
Patrick
T A
TA
Neuroscience Program, University of Illinois, Urbana 61801, USA.
Kranz
D M
DM
van Dyke
T A
TA
Roy
E J
EJ
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001345:Autoradiography; D001812:Blood-Brain Barrier; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016545:Choroid Plexus Neoplasms / Q000235:genetics / Q000378:metabolism*; D004806:Ependymoma / Q000235:genetics / Q000378:metabolism*; D058973:Folate Receptors, GPI-Anchored; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface