Mitochondrial and microsomal peripheral benzodiazepine receptors in human ovarian cancer xenografts.
To investigate whether the density of peripheral benzodiazepine receptors (PBR) in human ovarian tumors is related to the degree of histological differentiation and possibly elucidate their pathophysiology, PBR were measured in mitochondrial (m) and microsomal (p) fractions isolated from six different human ovarian carcinomas heterotransplanted into nude mice. A specific ligand PK11195 for PBR was employed and the density of binding sites and binding affinity (KD) were computed from Scatchard analysis. The PBR density in m-fractions was 3- to 4-fold higher than in p-fractions from all tumors. PBR density in both m- and p-fractions was highest in mucinous tumors with mid-high degree of differentiation. The density in serous tumor with mid-high differentiation was significantly lower than the mucinous tumor, but higher than the serous tumor with low degree of differentiation (OVCAR-3) in both m- and p-fractions. However, the PBR density in the undifferentiated tumor (IGROV1) was higher than in OVCAR-3. The KD values for PBR were very low ranging from 5.8 to 14.0 nM in all preparations. The KD values for p-fractions were generally lower than m-fractions and highly significant differences were observed in three of the six tumors. These data suggest two separate classes of PBR pertaining to m- and p-fractions and indicate that there is no clear relationship between PBR density and degree of differentiation.
Batra
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Department of Obstetrics and Gynecology, University Hospital, S-221 85 Lund, Sweden.
Larsson
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Boven
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D000818:Animals; D018291:Cystadenoma, Mucinous / Q000378:metabolism*; D018293:Cystadenoma, Serous / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D008861:Microsomes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D014183:Transplantation, Heterologous
D008024:Ligands; D011963:Receptors, GABA-A