G. Srkalovic et al., PRESENCE AND CHARACTERISTICS OF RECEPTORS FOR [D-TRP(6)]LUTEINIZING HORMONE-RELEASING HORMONE AND EPIDERMAL GROWTH-FACTOR IN HUMAN OVARIAN-CANCER, International journal of oncology, 12(3), 1998, pp. 489-498
This study was undertaken to establish the presence and characteristic
s of receptors for [D-Trp(6)]LH-RH on the membranes of human ovarian c
ancer. Specific binding of [I-125, D-Trp(6)]LH-RH was found in 29 of 3
7 (78.4%) ovarian cancers and in 6 of 11 (54.5%) non-malignant human o
varies. Ligand binding was dependent on time and plasma membrane conce
ntration in a fashion expected of a peptide hormone. Saturation, kinet
ic and displacement data were consistent with the presence of a highly
specific, single class of non-cooperative binding site. On the basis
of receptors affinity, LH-RH-receptor-positive ovarian cancers could b
e divided into two groups: high affinity group (K-d=2.7+/-0.60 nM; B-m
ax=0.46+/-0.07 pmol/mg membrane protein) comprising 55% of tumors, and
low affinity group (K-d=78.0+/-19.6 nM; B-max=9.44+/-2.68 pmol/mg mem
brane protein) which included 45% of tumors. LH-RH antagonist Cetrorel
ix showed an affinity to LH-RH receptors on ovarian cancers 14 times h
igher than the agonist [D-Trp(6)]LH-RH. Using I-125-epidermal growth f
actor, specific high affinity receptors were also detected in membrane
s from 13 of 24 (54%) ovarian cancers and 5 of 11 (45%) non-malignant
ovaries. The demonstration of LH-RH receptors in human ovarian cancers
provides a rationale for the use of therapeutic approaches based on L
H-RH analogues in this malignancy. The probable involvement of growth
factors in the development of ovarian cancers suggests the merit of tr
ying a combined therapy based on analogs of LH-RH and somatostatin for
this carcinoma.