Local Concentration of Folate Binding Protein GP38 in Sections of Human Ovarian Carcinoma by in Vitro Quantitative Autoradiography

Pei Yong Li, Silvana Del Vecchio, Rosa Fonti, Maria V. Carriero, Maria I. Potena, Gerardo Botti, Silvia Miotti, Secondo Lastoria, Sylvie Menard, Maria I. Colnaghi, Marco Salvatore

Research output: Contribution to journalArticlepeer-review

Abstract

Folate binding protein (FBP) GP38 is a membrane-associated glycoprotein that mediates the intracellular transport of folates. The enhanced expression of FBP in ovarian carcinomas provided a rational basis for clinical studies with specific monoclonal antibodies and some newly synthesized antifolate drugs. Because the outcome of these clinical studies ultimately depends on the degree of FBP expression, we measured the local concentration of FBP using 125I-MOv18 monoclonal antibody and quantitative autoradiography. Methods: Tissue sections from 37 specimens of ovarian carcinoma and 13 nonmalignant ovaries were incubated with increasing concentrations of 125I-MOv18 with and without an excess of unlabeled antibody. Tissue-bound radioactivity was measured by quantitative autoradiography. Results: Folate binding protein was found to be overexpressed in 91 % of nonmucinous ovarian carcinomas, with local concentrations ranging between 1.14 and 82.84 pmole/g. Adjacent tumor sections simultaneously studied with 125I-MOv18 and a 125I-labeled folic acid derivative showed matching and super-imposable regional distributions of bound radioactivity of the two radioligands, indicating that the antigen, specifically recognized by 125I-MOv18 in nonmucinous ovarian carcinomas, is capable of binding folates. Nonmalignant ovaries did not contain measurable amounts of antigen when assayed with 125MOv18 but showed a limited and specific binding of the 125I-folic acid derivative to tissue sections. The autoradiographic findings were confirmed by testing sections from mixtures of antigen-positive and antigen-negative cells, by immunoperoxidase staining with MOv18 on tumor sections and by biochemical identification of FBP in membrane fractions from tissue samples. Conclusion: Folate binding protein is overexpressed up to 80-90-fold in nonmucinous ovarian carcinomas compared with nonmalignant ovaries. Quantitation of FBP may provide a useful tool in the design of clinical studies with specific monoclonal antibodies and certain antifolate drugs that enter the cell through FBP.

Original languageEnglish
Pages (from-to)665-672
Number of pages8
JournalJournal of Nuclear Medicine
Volume37
Issue number4-6
Publication statusPublished - Apr 1996

Keywords

  • Folate binding protein
  • Folate receptor
  • GP38
  • MOv18
  • Ovarian carcinoma

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

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